Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H31N7O |
Molecular Weight | 493.6027 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCN(CC2=CC=C(C=C2)C(=O)NC3=CC(NC4=NC=CC(=N4)C5=CC=CN=C5)=C(C)C=C3)CC1
InChI
InChIKey=KTUFNOKKBVMGRW-UHFFFAOYSA-N
InChI=1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)
Molecular Formula | C29H31N7O |
Molecular Weight | 493.6027 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Imatinib (GLEEVEC®) is a tyrosine kinase inhibitor and antineoplastic agent that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive CML. Imatinib (GLEEVEC®) inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib (GLEEVEC®) inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.
CNS Activity
Originator
Approval Year
PubMed
Title | Date | PubMed |
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Sarcoma. | 2001 |
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The oncologic four-minute mile. | 2001 |
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Mechanisms of transformation by the BCR/ABL oncogene. | 2001 Apr |
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Recent advances in the molecular and cellular biology of chronic myeloid leukaemia: lessons to be learned from the laboratory. | 2001 Apr |
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Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. | 2001 Apr 1 |
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ARG tyrosine kinase activity is inhibited by STI571. | 2001 Apr 15 |
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Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. | 2001 Apr 5 |
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Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. | 2001 Apr 5 |
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Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. | 2001 Apr 5 |
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ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia: validating the promise of molecularly targeted therapy. | 2001 Aug |
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PDGF-beta receptor expression in the dorsocaudal brainstem parallels hypoxic ventilatory depression in the developing rat. | 2001 Aug |
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Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis. | 2001 Aug 1 |
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Chronic myelogenous leukemia. | 2001 Aug 22-29 |
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Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. | 2001 Aug 3 |
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Mechanisms of resistance imatinib (STI571) in preclinical models and in leukemia patients. | 2001 Feb |
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Molecular studies in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. | 2001 Jul |
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The role of Bcr-Abl in chronic myeloid leukemia and stem cell biology. | 2001 Jul |
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Cancer treatment. New drugs, new hope. | 2001 Jul |
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[STI571 and gastro intestinal stromal tumors]. | 2001 Jul |
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New leukemia drug receives FDA approval. | 2001 Jul |
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Anti-cancer drug success emerges from molecular biology origins. | 2001 Jul |
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New drug targets genetic malfunction in chronic myeloid leukemia. | 2001 Jul 15 |
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New-age drug meets resistance. | 2001 Jul 19 |
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After 30 years of laboratory work, a quick approval for STI571. | 2001 Jul 4 |
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From the Food and Drug Administration. | 2001 Jul 4 |
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ABL-specific tyrosine kinase inhibitor, STI571 in vitro, affects Ph-positive acute lymphoblastic leukemia and chronic myelogenous leukemia in blastic crisis. | 2001 Jun |
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Quick success for cancer kinase treatment. | 2001 Jun |
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Gleevec (STI-571) for chronic myeloid leukemia. | 2001 Jun 11 |
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Researchers optimistic about sea change in cancer treatment. | 2001 Jun 13 |
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Cancer research. Why some leukemia cells resist STI-571. | 2001 Jun 22 |
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Promising clinical trials on kinase inhibitor. | 2001 Mar |
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Sensitivity to the abl inhibitor STI571 in fresh leukaemic cells obtained from chronic myelogenous leukaemia patients in different stages of disease. | 2001 Mar |
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Chronic myeloid leukaemia. STI 571 magnifies the therapeutic dilemma. | 2001 Mar |
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Co-treatment with As2O3 enhances selective cytotoxic effects of STI-571 against Brc-Abl-positive acute leukemia cells. | 2001 May |
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STI571: a gene product-targeted therapy for leukemia. | 2001 May |
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Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. | 2001 May 1 |
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Tyrosine kinase inhibitor STI571 potentiates the pharmacologic activity of retinoic acid in acute promyelocytic leukemia cells: effects on the degradation of RARalpha and PML-RARalpha. | 2001 May 15 |
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Cancer's mechanics. Targeting errant cells. | 2001 May 21 |
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New hope for cancer. | 2001 May 28 |
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Progenitor cells from patients with advanced phase chronic myeloid leukaemia respond to STI571 in vitro and in vivo. | 2001 Nov |
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STI571: a magic bullet? | 2001 Oct |
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Requirement for Mdm2 in the survival effects of Bcr-Abl and interleukin 3 in hematopoietic cells. | 2001 Oct 15 |
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[Chronic myeloid leukemia and tyrosine kinase inhibitors]. | 2001 Sep |
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Improving the management of chronic myeloid leukaemia. | 2001 Sep |
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[Chronic myelogenous leukemia]. | 2001 Sep |
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Pharmacologic inhibition of the Bcr-Abl kinase with STI571: a novel, safe, and effective therapy for chronic myeloid leukemia. | 2001 Sep |
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Cancer treatment in the STI571 era: what will change? | 2001 Sep 15 |
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Roots of clinical resistance to STI-571 cancer therapy. | 2001 Sep 21 |
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Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation. | 2001 Sep 27 |
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Small molecule: large hopes. | 2001 Sep-Oct |
Sample Use Guides
The prescribed dose should be administered orally, with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
Route of Administration:
Oral
Imatinib (CGP 57148) was tested for growth inhibition of EGF-dependent BALB/MK cells, the H-ras-transformed T24 bladder carcinoma line, and IL-3-dependent growth of FDC-Pl cells. The compound showed only weak antiproliferative activity against these cell lines, with IC50 values of 12.7 uM, 9.4 uM, and 29.2 uM, respectively. However, when tested on v-abl-transformed PB-3c cells, incubation with CGP 57148 resulted in potent growth inhibition even in the presence of exogenous IL-3 (IC50 values, 0.11 uM without IL-3 and 0.9 uM with IL-3). Similar results were obtained using v-sis-transformed BALB/c 3T3 cells, which grow in response to autocrine PDGF production (IC50, 0.33 uM).
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Oct 21 20:54:26 UTC 2019
by
admin
on
Mon Oct 21 20:54:26 UTC 2019
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Record UNII |
BKJ8M8G5HI
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Record Status |
Validated (UNII)
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Record Version |
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Common Name | English | ||
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Classification Tree | Code System | Code | ||
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WHO-ATC |
L01XE01
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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EMA ASSESSMENT REPORTS |
IMANTINIB TEVA (AUTHORIZED: LEUKEMIA, , MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)
Created by
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LIVERTOX |
500
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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EU-Orphan Drug |
EU/3/14/1357
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FDA ORPHAN DRUG |
208905
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NDF-RT |
N0000175076
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NCI_THESAURUS |
C155700
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FDA ORPHAN DRUG |
303810
Created by
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EMA ASSESSMENT REPORTS |
IMANTINIB ACTAVIS (AUTHORIZED: LEUKEMIA, , MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE)
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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EMA ASSESSMENT REPORTS |
GLIVEC (AUTHORIZED: GASTROINTESTINAL STROMAL TUMORS)
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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EMA ASSESSMENT REPORTS |
IMATINIB MEDAC (AUTHORIZED DERMATOFIBROSARCOMA)
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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FDA ORPHAN DRUG |
140100
Created by
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NDF-RT |
N0000175605
Created by
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EMA ASSESSMENT REPORTS |
IMANTIB ACCORD (AUTHORIZED: DERMATOFIBROSARCOMA)
Created by
admin on Mon Oct 21 20:54:26 UTC 2019 , Edited by admin on Mon Oct 21 20:54:26 UTC 2019
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WHO-VATC |
QL01XE01
Created by
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Code System | Code | Type | Description | ||
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DB00619
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PRIMARY | |||
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5291
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PRIMARY | |||
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C097613
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PRIMARY | |||
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SUB25387
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PRIMARY | |||
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152459-95-5
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PRIMARY | |||
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282388
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PRIMARY | RxNorm | ||
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IMATINIB
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PRIMARY | |||
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8031
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PRIMARY | |||
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152459-95-5
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PRIMARY | |||
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C62035
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PRIMARY | |||
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M6213
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PRIMARY | Merck Index | ||
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5687
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PRIMARY | |||
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CHEMBL941
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PRIMARY | |||
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152459-95-5
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PRIMARY |
Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TRANSPORTER -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR |
Gao et al. reported that in vitro, imatinib (1 M) increases the intracellular concentration of vincristine and mitoxantrone in cells overexpressing ABCB1 and ABCG2, respectively.
INHIBITOR
CLINICALLY SIGNIFICANT
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TRANSPORTER -> SUBSTRATE | |||
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR |
COMPETITIVE INHIBITOR
Ki
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TARGET -> INHIBITOR |
Kd; Target: KIT
INHIBITOR
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METABOLIC ENZYME -> SUBSTRATE |
COMPETITIVE INHIBITOR
Ki
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR |
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR |
COMPETITIVE INHIBITOR
Ki
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RESISTANT TARGET->INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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RESISTANT TARGET->INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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BINDER->LIGAND |
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TRANSPORTER -> SUBSTRATE |
Related Record | Type | Details | ||
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PRODRUG -> METABOLITE ACTIVE | |||
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METABOLITE ACTIVE -> PARENT |
CAN BE RESPONSIBLE FOR UP 80 OR THE METABOLISM AS CYP3A4 GETS INHIBITED
MAJOR
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METABOLITE ACTIVE -> PARENT |
AUTOINHIBITION
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PRODRUG -> METABOLITE ACTIVE |
Related Record | Type | Details | ||
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ACTIVE MOIETY |