FOSTEMSAVIR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H26N7O8P
Molecular Weight	583.4908
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cc1ncn(-c2c3c(c(cn3COP(=O)(O)O)C(=O)C(=O)N4CCN(CC4)C(=O)c5ccccc5)c(cn2)OC)n1

InChI

InChIKey=SWMDAPWAQQTBOG-UHFFFAOYSA-N

InChI=1S/C25H26N7O8P/c1-16-27-14-32(28-16)23-21-20(19(39-2)12-26-23)18(13-31(21)15-40-41(36,37)38)22(33)25(35)30-10-8-29(9-11-30)24(34)17-6-4-3-5-7-17/h3-7,12-14H,8-11,15H2,1-2H3,(H2,36,37,38)

HIDE SMILES / InChI

Description
Sources: https://aidsinfo.nih.gov/drugs/508/fostemsavir/0/patient | https://www.hiv.uw.edu/page/treatment/drugs/fostemsavir | https://www.ncbi.nlm.nih.gov/pubmed/27922453

Fostemsavir (BMS-663068) is an investigational attachment inhibitor with a unique mechanism of action. It is a prodrug of temsavir, which binds to HIV envelope glycoprotein 120 (gp120), thereby preventing viral attachment to the host CD4 cell surface receptor. In the absence of effective binding of HIV gp120 with the host CD4 receptor, HIV does not enter the host cell. Because fostemsavir has a novel mechanism of action, the drug should have full activity against HIV strains that have developed resistance to other classes of antiretroviral medications. In a phase 2b study of treatment-experienced individuals, fostemsavir appeared to be well tolerated. Phase 3 studies are ongoing.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus 1 32 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22547625	Inhibitor 7687

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 140 Sources: http://adisinsight.springer.com/drugs/800031504 https://clinicaltrials.gov/ct2/show/NCT02362503	Primary		Phase III 650	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1770 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: other antiretroviral drugs	other antiretroviral drugs	TEMSAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.39 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22896665/	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TEMSAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED
2.55 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg single, oral dose: 1200 mg route of administration: oral experiment type: single co-administered:		TEMSAVIR plasma	Homo sapiens
3.18 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens
3.38999999999999 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens
3.61 ug/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
12900 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	600 mg 2 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered: other antiretroviral drugs	other antiretroviral drugs	TEMSAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
42.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22896665/	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TEMSAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED
13.8 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg single, oral dose: 1200 mg route of administration: oral experiment type: single co-administered:		TEMSAVIR plasma	Homo sapiens
19.5 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens
22.5 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens
42.6 ug*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01009814	1200 mg 1 times / 12 hours multiple, oral dose: 1200 mg route of administration: oral experiment type: multiple co-administered:		TEMSAVIR plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		TEMSAVIR plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
26.9% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		TEMSAVIR plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: optimized background therapy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	unhealthy, 17-43 years n = 271 Health Status: unhealthy Condition: HIV-1 infection Age Group: 17-43 years Sex: M+F Population Size: 271 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf	Disc. AE: Immune reconstitution inflammatory syndrome... Other AEs: Nausea, Diarrhea... AEs leading to discontinuation/dose reduction: Immune reconstitution inflammatory syndrome (grade 3, 3%) Other AEs: Nausea (grade 1-4, 10%) Diarrhea (grade 1-4, 4%) Headache (grade 1-4, 4%) Abdominal pain (grade 1-4, 3%) Dyspepsia (grade 1-4, 3%) Fatigue (grade 1-4, 3%) Rash (grade 1-4, 3%) Sleep disturbance (grade 1-4, 3%) Immune reconstitution inflammatory syndrome (grade 1-4, 2%) Somnolence (grade 1-4, 2%) Vomiting (grade 1-4, 2%) ALT increased (grade 3-4, 5%) AST increased (grade 3-4, 4%) Direct bilirubin increased (grade 3, 7%) Bilirubin increased (grade 3-4, 3%) Creatinine increased (grade 3-4, 19%) Creatine kinase increased (grade 3-4, 2%) Hemoglobin decreased (grade 3-4, 6%) Hyperglycemia (grade 3-4, 4%) Lipase increased (grade 3-4, 5%) Neutrophils reduced (grade 3-4, 4%) Blood triglycerides increased (grade 3-4, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: ritonavir(100 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	healthy, 18-49 years n = 18 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	Other AEs: Scleral icterus, Abdominal pain... Other AEs: Scleral icterus (5.6%) Abdominal pain (5.6%) Nausea (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Co-administed with:: atazanavir(300 mg; oral; 1/day) ritonavir(100 mg; oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	Other AEs: Scleral icterus, Abdominal pain... Other AEs: Scleral icterus (27.8%) Abdominal pain (11.1%) Headache (13.9%) Dizziness (5.6%) Nausea (8.3%) Musculoskeletal chest pain (2.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	healthy, 18-49 years n = 36 Health Status: healthy Age Group: 18-49 years Sex: M+F Population Size: 36 Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/	Other AEs: Headache... Other AEs: Headache (5.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/25870057/
1050 mg 2 times / day steady, oral (mean) Studied dose Dose: 1050 mg, 2 times / day Route: oral Route: steady Dose: 1050 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	unhealthy, adults n = 200 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 200 Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	Other AEs: Headache... Other AEs: Headache (grade 1, 14%) Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/
1200 mg 1 times / day steady, oral Studied dose Dose: 1200 mg, 1 times / day Route: oral Route: steady Dose: 1200 mg, 1 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	Disc. AE: Disseminated tuberculosis, Back pain... AEs leading to discontinuation/dose reduction: Disseminated tuberculosis (2%) Back pain (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/
400 mg 2 times / day steady, oral Studied dose Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	unhealthy, adults n = 50 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	Disc. AE: Ischaemia... AEs leading to discontinuation/dose reduction: Ischaemia (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/
800 mg 2 times / day steady, oral Studied dose Dose: 800 mg, 2 times / day Route: oral Route: steady Dose: 800 mg, 2 times / day Co-administed with:: raltegravir and tenofovir disoproxil fumarate Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	unhealthy, adults n = 49 Health Status: unhealthy Condition: HIV-1 infection Age Group: adults Sex: M+F Population Size: 49 Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/	Disc. AE: Bone tuberculosis, Acute renal failure... AEs leading to discontinuation/dose reduction: Bone tuberculosis (2%) Acute renal failure (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/26423650/
2400 mg 2 times / day steady, oral Highest studied dose Dose: 2400 mg, 2 times / day Route: oral Route: steady Dose: 2400 mg, 2 times / day Sources: https://www.fda.gov/media/140641/download	healthy n = 15 Health Status: healthy Population Size: 15 Sources: https://www.fda.gov/media/140641/download	Other AEs: QT interval prolonged... Other AEs: QT interval prolonged Sources: https://www.fda.gov/media/140641/download

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1171 inducer 657	substrate 865 inhibitor 1318	substrate 1038 inhibitor 1421	inhibitor 1359

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 698 OATP1B3 613 CYP 97 UGT 29 BCRP 574 MATE2 258 CYP1A2 1268 CYP2B6 679 CYP2C8 761 CYP2C19 1215 CYP2A6 594 UGT1A1 174 UGT1A4 67 UGT1A9 102 UGT1A6 94 UGT2B7 130 P-gp 1087 OAT1 547 OAT3 570 MATE1 290 MRP2 341 NTCP 31 OCT2 582 BSEP 363 OCT1 473	CYP3A 154 P-gp 1222 BCRP 461 esterase 63 UGT 160 CYP1A1 302 CYP1A2 892 CYP2A6 452 CYP1B1 82 CYP2B6 575 CYP2C8 586 CYP2C19 830 FMO3 49 CYP4A11 90 CYP2E1 567 CYP3A5 346	CYP1A2 618 CYP2B6 486

Drug as perpetrator

Target	Modality	Activity	Metabolite
OAT1 551	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 182.0	no [IC50 110 uM]	temsavir 4
OCT1 488	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 184.0	no [IC50 32.8 uM]	temsavir 4
UGT1A6 126	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >10 uM]	temsavir 4
UGT1A9 107	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >10 uM]	temsavir 4
UGT2B7 138	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 177.0	no [IC50 >10 uM]
UGT2B7 138	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 177.0	no [IC50 >10 uM]	temsavir 4
OCT2 583	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 184.0	no [IC50 >100 uM]	temsavir 4
UGT1A1 219	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]
UGT1A1 219	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]	temsavir 4
UGT1A4 70	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]
UGT1A4 70	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]	temsavir 4
UGT1A6 126	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]
UGT1A9 107	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 176.0	no [IC50 >100 uM]
BCRP 639	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 181.0	no [IC50 >250 uM]
P-gp 1253	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 181.0	no [IC50 >250 uM]
CYP1A2 1406	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 174.0	no [IC50 >40 uM]	temsavir 4
CYP2A6 625	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 175.0	no [IC50 >40 uM]	temsavir 4
CYP2B6 845	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 174.0	no [IC50 >40 uM]	temsavir 4
CYP2C19 1277	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 175.0	no [IC50 >40 uM]	temsavir 4
CYP2C8 810	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 174.0	no [IC50 >40 uM]	temsavir 4
CYP2C9 1362	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 174.0	no [IC50 >40 uM]	temsavir 4
CYP2D6 1455	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 175.0	no [IC50 >40 uM]	temsavir 4
CYP3A4 1461	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 175.0	no [IC50 >40 uM]	temsavir 4
BSEP 364	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 184.0	no [IC50 >50 uM]	temsavir 4
MRP2 421	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 183.0	no [IC50 >50 uM]	temsavir 4
NTCP 32	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 183.0	no [IC50 >50 uM]	temsavir 4
OAT3 572	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 182.0	no [IC50 >50 uM]	temsavir 4
P-gp 1253	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 181.0	no [Inhibition 25 uM]	temsavir 4
CYP 131	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36.0	no	temsavir 4
CYP1A2 1406	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 177.0	no	temsavir 4
CYP2B6 845	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 178.0	no	temsavir 4
CYP3A4 1461	inducer 1333 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 178.0	no	temsavir 4
UGT 49	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36.0	no	temsavir 4
MATE2 258	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36, 183	yes [IC50 12.2 uM]	temsavir 4
MATE1 291	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 182.0	yes [IC50 18.5 uM]	temsavir 4
BCRP 639	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36, 114	yes	temsavir 4
OATP1B1 713	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36, 114, 180	yes	temsavir 4
OATP1B3 622	inhibitor 2612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 36, 114, 181	yes	temsavir 4

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT 160	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35.0	minor	temsavir 4
CYP1A1 302	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP1A2 892	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP1B1 82	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2A6 452	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2B6 575	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2C19 830	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2C8 586	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2C9 865	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2D6 1038	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP2E1 567	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP3A5 346	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
CYP4A11 90	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
FMO3 49	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 173.0	no	temsavir 4
BCRP 461	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35, 179	yes	temsavir 4
P-gp 1222	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35, 179	yes	temsavir 4
esterase 63	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35.0	yes	temsavir 4
CYP3A 154	substrate 2751 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35, 111, 112, 113	yes	temsavir 4	yes (co-administration study) Comment: coadministration of fostemsavir with rifampin significantly decreases temsavir plasma concentrations, reduced temsavir AUC by 80%; coadministration of fostemsavir with drugs that are strong CYP3A inducers result in decreased concentrations of temsavir. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 35, 111, 112, 113

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1391	inhibitor 1373 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212950Orig1s000IntegratedR.pdf Page: 69.0		temsavir 4

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY575616	https://www.001chemical.com/chem/864953-29-7
AA Blocks	AA00GTZ5	https://www.aablocks.com/goods/Goods/detail?id=AA00GTZ5
AK Scientific, Inc. (AKSCI)	3502AH	http://www.aksci.com/item_detail.php?cat=3502AH
Acadechem	ACDS-0781672	http://acadechemical.com/product/229218
Achemtek	0102-013953	http://www.achemtek.com/864953-29-7
Adooq BioScience	A15025	https://www.adooq.com/bms-663068.html
Ambinter	Amb22396014	http://www.ambinter.com/reference/22396014
Angene	AGN-PC-0WCXR0	http://www.angenechemical.com/productshow/AGN-PC-0WCXR0.html
Aurora Fine Chemicals LLC	A24.141.513	http://online.aurorafinechemicals.com/info?ID=A24.141.513
Aurum Pharmatech LLC	W-5998	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5998
BOC Sciences	864953-29-7	https://www.bocsci.com/bms-663068-cas-864953-29-7-item-84-463659.html
BioChemPartner	BCP13226	http://www.biochempartner.com/864953-29-7-BCP13226
BioCrick	BCC1428	http://www.biocrick.com/BMS-663068-BCC1428.html
Boerchem	BC600763	http://www.boerchem.com/?product_43597.html
Chem Scene	CS-1059	http://www.chemscene.com/864953-29-7.html
Chemspace	CSSB00137314448	https://chem-space.com/CSSB00137314448
DC Chemicals	DC8163	http://www.dcchemicals.com/product_show-Fostemsavir_BMS_663068_.html
Excenen	EX-A1973	https://www.excenen.com/searchresultlist.php?id=864953-29-7
Hairui	FOXF012	http://www.hairuichem.com/en/product/864953-29-7.html
MedChem Express	HY-15440A	https://www.medchemexpress.com/BMS-663068.html
Molcore	MC575616	https://www.molcore.com/product/864953-29-7
MuseChem	I005194	https://www.musechem.com/product/I005194.html
Selleck Chemicals	S7220	http://www.selleckchem.com/products/bms-663068.html
Smolecule	S528400	http://www.smolecule.com/products/s528400
Synblock Inc	SB11250	http://www.synblock.com/product/864953-29-7.html
THE BioTek	bt-268684	https://www.thebiotek.com/product/inhibitors/bt-268684
THE BioTek	bt-342630	https://www.thebiotek.com/product/others/bt-342630
THE BioTek	bt-464747	https://www.thebiotek.com/product/others/bt-464747

PubMed

Title	Date	PubMed
Safety and efficacy of the HIV-1 attachment inhibitor prodrug BMS-663068 in treatment-experienced individuals: 24 week results of AI438011, a phase 2b, randomised controlled trial.	2015 Oct	26423650
Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529.	2016 May	26902761
Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in antiretroviral-experienced subjects: week 48 analysis of AI438011, a Phase IIb, randomized controlled trial.	2017	27922453
[What can new substances offer?]	2017 Jun	28597267
Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry Inhibitors and HIV Therapy.	2017 Oct 16	28738768

Patents

Sample Use Guides

In Vivo Use Guide

A phase 2b trial enrolled treatment-experienced adults with HIV infection and randomized study subjects to one of four doses of fostemsavir (400 mg twice daily, 800 mg twice daily, 600 mg once daily, or 1200 mg once daily).

Route of Administration: Oral

In Vitro Use Guide

BMS-626529 (an active moiety of BMS-663068) exhibits an average EC50 against LAI of 0.7 +/-0.4 nM.

Name

Type

Language

FOSTEMSAVIR

Official Name

English

FOSTEMSAVIR [INN]

Common Name

English

BMS-663068

Code

English

(3-((4-BENZOYLPIPERAZIN-1-YL)-OXOACETYL)-4-METHOXY- 7-(3-METHYL-1H-1,2,4-TRIAZOL-1-YL)-1H-PYRROLO(2,3-C)PYRIDIN- 1-YL)METHYL DIHYDROGEN PHOSPHATE

Systematic Name

English

FOSTEMSAVIR [USAN]

Common Name

English

PIPERAZINE, 1-BENZOYL-4-((4-METHOXY-7-(3-METHYL-1H-1,2,4-TRIAZOL-1-YL)-1-((PHOSPHONOOXY)METHYL)-1H-PYRROLO(2,3-C)PYRIDIN-3-YL)OXOACETYL)-

Systematic Name

English

FOSTEMSAVIR [WHO-DD]

Common Name

English

BMS-663068 FREE ACID

Common Name

English

Code System Code Type Description

PUBCHEM

11319217