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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C26H33FN4O3S.H2O
Molecular Weight 1019.273
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LCL-161 HEMIHYDRATE

SMILES

O.CN[C@@H](C)C(=O)N[C@@H](C1CCCCC1)C(=O)N2CCC[C@H]2C3=NC(=CS3)C(=O)C4=CC=C(F)C=C4.CN[C@@H](C)C(=O)N[C@@H](C5CCCCC5)C(=O)N6CCC[C@H]6C7=NC(=CS7)C(=O)C8=CC=C(F)C=C8

InChI

InChIKey=XRUNRQMZUXENTM-FKTCFRFMSA-N
InChI=1S/2C26H33FN4O3S.H2O/c2*1-16(28-2)24(33)30-22(17-7-4-3-5-8-17)26(34)31-14-6-9-21(31)25-29-20(15-35-25)23(32)18-10-12-19(27)13-11-18;/h2*10-13,15-17,21-22,28H,3-9,14H2,1-2H3,(H,30,33);1H2/t2*16-,21-,22-;/m00./s1

HIDE SMILES / InChI
Molecular Formula C26H33FN4O3S
Molecular Weight 500.629
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800031959 | https://www.ncbi.nlm.nih.gov/pubmed/25113756

Ipatasertib (LCL161) binds to inhibitors of apoptosis proteins (IAPs) with high affinity and initiates the destruction of cIAP1 and cIAP2, which further induces apoptosis via caspase activation. Ipatasertib is advancing in clinical development including five Phase 2 trials in patients with Breast cancer, Multiple myeloma, Myelofibrosis, Small cell lung cancer and Ovarian cancer. The most common LCL161-related adverse events were nausea and vomiting.

Originator

Novartis
177
Curator's Comment: synthesized by Novartis Pharma AG, developed by Chen K.F. et al in National Taiwan University Hospital https://www.ncbi.nlm.nih.gov/pubmed/22580047 # Novartis

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
Inhibitor
8504
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase I
438
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2350 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25113756
1800 mg 1 times / week single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2350 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25113756
1800 mg single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32081 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25113756
1800 mg 1 times / week single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
32081 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25113756
1800 mg single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.9 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/25113756
1800 mg 1 times / week single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.9 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/25113756
1800 mg single, oral
dose: 1800 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LCL-161 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3000 mg 1 times / week multiple, oral
Highest studied dose
Dose: 3000 mg, 1 times / week
Route: oral
Route: multiple
Dose: 3000 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
DLT: Cytokine release syndrome...
Dose limiting toxicities:
Cytokine release syndrome (grade 4, 50%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
1800 mg 1 times / week multiple, oral
RP2D
Dose: 1800 mg, 1 times / week
Route: oral
Route: multiple
Dose: 1800 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
2100 mg 1 times / week multiple, oral
Studied dose
Dose: 2100 mg, 1 times / week
Route: oral
Route: multiple
Dose: 2100 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
DLT: Cytokine release syndrome...
Dose limiting toxicities:
Cytokine release syndrome (grade 3, 50%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
AEs

AEs

AESignificanceDosePopulation
Cytokine release syndrome grade 4, 50%
DLT, Disc. AE
3000 mg 1 times / week multiple, oral
Highest studied dose
Dose: 3000 mg, 1 times / week
Route: oral
Route: multiple
Dose: 3000 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
Cytokine release syndrome grade 3, 50%
DLT, Disc. AE
2100 mg 1 times / week multiple, oral
Studied dose
Dose: 2100 mg, 1 times / week
Route: oral
Route: multiple
Dose: 2100 mg, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/25113756
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252
inhibitor
2438
inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP3A
227

P-gp
1741
P-gp
2052
CYP3A
142
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A
317
 moderate
CYP2C9
2497
 no
CYP2D6
2546
 no
CYP3A
317
 yes [Ki 0.797 uM]
yes (co-administration study)
Comment: Increased midazolam Cmax and AUCinf by 3.22-fold and 9.32-fold.
CYP3A4
2633
 yes
P-gp
1932
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
2052
 no
PubMed

PubMed

TitleDatePubMed
Benzazepinones and benzoxazepinones as antagonists of inhibitor of apoptosis proteins (IAPs) selective for the second baculovirus IAP repeat (BIR2) domain.
2013-10-24
Inhibition of Bcl-2 improves effect of LCL161, a SMAC mimetic, in hepatocellular carcinoma cells.
2012-08-01
Initial testing (stage 1) of LCL161, a SMAC mimetic, by the Pediatric Preclinical Testing Program.
2012-04
Smac mimetics: implications for enhancement of targeted therapies in leukemia.
2010-12
Patents

Patents

20100056467
2
US8906936 B2
2
WO2013043591 A1
2

Sample Use Guides

In Vivo Use Guide
1800 mg dose, administered as a single agent once weekly
Route of Administration: Oral
In Vitro Use Guide
LCL161 showed antiproliferative effects and reduced cell viability significantly in Hep3B (IC50 10.23 uM) and PLC5 (IC50 19.19 uM) cells in a dosedependent manner. However, Sk-Hep1 (IC50 223.55 uM) and Huh-7 cells (IC50 227.77 uM) showed resistance to LCL161 as measured by cell viability.
Substance Class Chemical
Created
by admin
on Tue Apr 01 20:31:47 GMT 2025
Edited
by admin
on Tue Apr 01 20:31:47 GMT 2025
Record UNII
YM7FH0V7ZO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LCL-161 HEMIHYDRATE
Common Name English
NVP-LCL 161 HEMIHYDRATE
Preferred Name English
PROPANAMIDE, N-((1S)-1-CYCLOHEXYL-2-((2S)-2-(4-(4-FLUOROBENZOYL)-2-THIAZOLYL)-1-PYRROLIDINYL)-2-OXOETHYL)-2-(METHYLAMINO)-, HYDRATE (2:1), (2S)-
Systematic Name English
Code System Code Type Description
FDA UNII
YM7FH0V7ZO
Created by admin on Tue Apr 01 20:31:47 GMT 2025 , Edited by admin on Tue Apr 01 20:31:47 GMT 2025
PRIMARY
PUBCHEM
137528282
Created by admin on Tue Apr 01 20:31:47 GMT 2025 , Edited by admin on Tue Apr 01 20:31:47 GMT 2025
PRIMARY
CAS
1263876-34-1
Created by admin on Tue Apr 01 20:31:47 GMT 2025 , Edited by admin on Tue Apr 01 20:31:47 GMT 2025
PRIMARY
Related Record Type Details
Structure of LCL-161
ANHYDROUS->SOLVATE
Structure of LCL-161
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of LCL-161
ACTIVE MOIETY
NIH
NCATS
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