SAR-405838

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H34Cl2FN3O3
Molecular Weight	562.503
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C[C@@H]1N[C@H]([C@H](C2=C(F)C(Cl)=CC=C2)[C@]13C(=O)NC4=C3C=CC(Cl)=C4)C(=O)N[C@H]5CC[C@H](O)CC5

InChI

InChIKey=IDKAKZRYYDCJDU-HBMMIIHUSA-N

InChI=1S/C29H34Cl2FN3O3/c1-28(2,3)14-22-29(19-12-7-15(30)13-21(19)34-27(29)38)23(18-5-4-6-20(31)24(18)32)25(35-22)26(37)33-16-8-10-17(36)11-9-16/h4-7,12-13,16-17,22-23,25,35-36H,8-11,14H2,1-3H3,(H,33,37)(H,34,38)/t16-,17-,22-,23-,25+,29+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25145672
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/28324749

SAR-405838 is an inhibitor of the interaction between the oncoprotein murine double minute 2 (MDM2) and p53. SAR-405838 was investigated in phase I clinical trials in patients with locally advanced/metastatic solid tumor with wild-type TP53 or with TP53 mutation prevalence below 40%. SAR-405838 had an acceptable safety profile with limited activity in patients with advanced solid tumors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
p53-binding protein Mdm-2 9 Target ID: CHEMBL5023 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25145672	Inhibitor 8297		0.88 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25145672	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1510 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2170 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4590 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	1800 mg 1 times / week multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
4651 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31619389	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	SAR-405838 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
13000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
32300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
78000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	1800 mg 1 times / week multiple, oral dose: 1800 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
61195 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31619389	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	SAR-405838 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
18.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28324749	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	SAR-405838 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.26 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31619389	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	SAR-405838 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.059% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31619389	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		SAR-405838 plasma	Mus musculus population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P009C62	https://www.1pchem.com/search?query=1P009C62
Cayman Chemical	17473	http://www.caymanchem.com/app/template/Product.vm/catalog/17473
MolPort	MolPort-044-561-439	https://www.molport.com/shop/molecule-link/MolPort-044-561-439
MolPort	MolPort-046-702-061	https://www.molport.com/shop/molecule-link/MolPort-046-702-061
Molnova	M11218	https://www.molnova.com/en/serch-list.html?keywords=M11218
eMolecules	64090097	https://orderbb.emolecules.com/search/#?query=64090097

PubMed

Title	Date	PubMed
SAR405838: an optimized inhibitor of MDM2-p53 interaction that induces complete and durable tumor regression.	2014 Oct 15	25145672
A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours.	2017 May	28324749

Patents

Sample Use Guides

In Vivo Use Guide

In phase I clinical trials SAR405838 was administered orally once daily or once weekly. The MTD for QD administration was 300 mg.

Route of Administration: Oral

In Vitro Use Guide

Cell growth inhibition activity was determined in a water-soluble tetrazolium (WST)-based assay. SAR405838 inhibits cell growth in cancer cell lines of diverse tumor types with wild-type p53 and displays high selectivity over cancer cell lines with mutated or deleted p53. IC50 for cell growth ranged from 0.092 to 0.2 uM.

Name

Type

Language

SAR-405838

Common Name

English

(2'S,3'R,4'S,5'R)-6-CHLORO-4'-(3-CHLORO-2-FLUORO-PHENYL)-2'-(2,2-DIMETHYL-PROPYL)-2-OXO-1,2-DIHYDRO-SPIRO (INDOLE-3,3'-PYRROLIDINE)-5'-CARBOXYLIC ACID (TRANS-4-HYDROXY-CYCLOHEXYL)-AMIDE

Systematic Name

English

SAR 405838 [WHO-DD]

Common Name

English

SPIRO(3H-INDOLE-3,3'-PYRROLIDINE)-5'-CARBOXAMIDE, 6-CHLORO-4'-(3-CHLORO-2-FLUOROPHENYL)-2'-(2,2-DIMETHYLPROPYL)-1,2-DIHYDRO-N-(TRANS-4-HYDROXYCYCLOHEXYL)-2-OXO-, (2'S,3R,4'S,5'R)-

Systematic Name

English

SAR405838

Code

English

(2'S,3R,4'S,5'R)-6-CHLORO-4'-(3-CHLORO-2-FLUOROPHENYL)-2'-(2,2-DIMETHYLPROPYL)-N-(TRANS-4-HYDROXYCYCLOHEXYL)-2-OXO-1,2-DIHYDROSPIRO(INDOLE-3,3'-PYRROLIDINE)-5'-CARBOXAMIDE

Systematic Name

English

MI-77301

Code

English

Code System Code Type Description

FDA UNII

8570LZ3RCA