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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H26N4O3
Molecular Weight 406.4784
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAMOTOLISIB

SMILES

C[C@@]([H])(Cn1c2c3cc(ccc3ncc2n(C)c1=O)-c4cc(cnc4)C(C)(C)O)OC

InChI

InChIKey=ACCFLVVUVBJNGT-AWEZNQCLSA-N
InChI=1S/C23H26N4O3/c1-14(30-5)13-27-21-18-9-15(16-8-17(11-24-10-16)23(2,3)29)6-7-19(18)25-12-20(21)26(4)22(27)28/h6-12,14,29H,13H2,1-5H3/t14-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created using several sources including: http://www.lillyoncologypipeline.com/molecule/pi-3-k-m-tor-dual-inhibitor/overview; https://www.google.com/patents/WO2012097039A1|https://clinicaltrials.gov/ct2/show/NCT02407054|https://clinicaltrials.gov/ct2/show/NCT02443337|https://clinicaltrials.gov/ct2/show/NCT02549989

LY3023414, an investigational drug, is a small molecule that that demonstrates activity against PI3K, mTOR, and DNA-PK in tumor cells, thereby inducing cell-cycle effects and inhibiting cancer cell viability. As shown in vitro LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway, one of the most frequently mutated pathways in cancer, leading to cancer progression and resistance to existing treatments. Downstream target inhibition by LY3023414 occurs rapidly via an intermittent “on/off” mechanism that may enhance the drug's clinical tolerability, which may in turn allow LY3023414 to overcome some of the toxicities associated with PI3K/mTOR inhibitors and potentially reduce the emergence of feedback mechanisms leading to resistance. The physicochemical and absorption properties of LY3023414 are favorable, as evidenced by the molecule's high solubility across a wide pH range and high oral bioavailability. On the basis of these findings, LY3023414 is currently being evaluated in clinical trials in patients with advanced cancer such as metastatic prostate cancer and non-small cell lung cancer in combination with other chemotherapeutic agents and in endometrial cancer as a monotherapy.

Originator

Curator's Comment:: # Eli Lilly

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak
yes (co-administration study)
Comment: Increased midazolam AUCinf by 46%.
yes [IC50 0.6513 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Genomic profiling is predictive of response to cisplatin treatment but not to PI3K inhibition in bladder cancer patient-derived xenografts.
2016 Nov 22
Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth.
2016 Oct
PI3K/mTOR Dual Inhibitor, LY3023414, Demonstrates Potent Antitumor Efficacy Against Esophageal Adenocarcinoma in a Rat Model.
2017 Jul
Patents

Sample Use Guides

200 mg LY3023414 twice daily in patients with recurrent or persistent endometrial cancer
Route of Administration: Oral
The ability of LY3023414 to inhibit cancer cell proliferation was evaluated in 32 human cancer cell lines from different tumor types in culture after LY3023414 treatment for 2 to 3 cell doublings in dose–response studies.LY3023414 demonstrated potent single-agent activity and IC50 values below 122 nmol/L in half of the cell lines tested. Among the more sensitive cell lines were ones originating from breast cancer (4 of 4 tested) and mesothelioma (5 of 6 tested), whereas none of the lung or colon cancer cell lines tested appeared to be highly sensitive.
Name Type Language
SAMOTOLISIB
USAN   INN  
Official Name English
LY3023414
Code English
PI3K/MTOR INHIBITOR LY3023414
Common Name English
2H-IMIDAZO(4,5-C)QUINOLIN-2-ONE, 1,3-DIHYDRO-8-(5-(1-HYDROXY-1-METHYLETHYL)-3-PYRIDINYL)-1-((2S)-2-METHOXYPROPYL)-3-METHYL-
Systematic Name English
8-(5-(2-HYDROXYPROPAN-2-YL)PYRIDIN-3-YL)-1-((2S)-2-METHOXYPROPYL)-3-METHYL-1,3-DIHYDRO-2H-IMIDAZO(4,5-C)QUINOLIN-2-ONE
Systematic Name English
LY-3023414
Code English
SAMOTOLISIB [INN]
Common Name English
SAMOTOLISIB [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
Code System Code Type Description
INN
10889
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
DRUG BANK
DB12167
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL3544999
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
PUBCHEM
57519748
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
CAS
1386874-06-1
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
FDA UNII
C88817F47Y
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY
NCI_THESAURUS
C121817
Created by admin on Sat Jun 26 16:39:01 UTC 2021 , Edited by admin on Sat Jun 26 16:39:01 UTC 2021
PRIMARY