GDC-0917

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H36N6O4S
Molecular Weight	564.699
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN[C@@H](C)C(=O)N[C@@H](C1CCCCC1)C(=O)N2CCC[C@H]2C(=O)NC3=C(N=C(S3)C4=NC=CO4)C5=CC=CC=C5

InChI

InChIKey=HSHPBORBOJIXSQ-HARLFGEKSA-N

InChI=1S/C29H36N6O4S/c1-18(30-2)24(36)32-23(20-12-7-4-8-13-20)29(38)35-16-9-14-21(35)25(37)34-27-22(19-10-5-3-6-11-19)33-28(40-27)26-31-15-17-39-26/h3,5-6,10-11,15,17-18,20-21,23,30H,4,7-9,12-14,16H2,1-2H3,(H,32,36)(H,34,37)/t18-,21-,23-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C29H36N6O4S
Molecular Weight	564.699
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27076626
Curator's Comment: The description was created based on several sources, including http://www.google.ch/patents/US20130172264 | https://www.ncbi.nlm.nih.gov/pubmed/24041744 | https://www.ncbi.nlm.nih.gov/pubmed/24041744

GDC-0917 (CUDC-427) is an orally available, monovalent mimetic of the second mitochondrial-derived activator of caspases (Smac/DIABLO) and inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0917 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2. This inhibits the activities of these IAPs and promotes the induction of apoptosis through apoptotic signaling pathways. GDC-0917 demonstrated single-agent antitumor activity in mouse xenograft models bearing subcutaneous MDA-MB-231 tumors. In addition, CUDC-427 demonstrated additive activity in combination with chemotherapeutic agents and tumor necrosis factor apoptosis-inducing ligand (TRAIL) receptor targeting antibodies in xenograft tumor models. Preclinical safety and pharmacokinetic testing established an expected therapeutic range of doses as well as elucidated possible toxicities including inflammatory cytokine and chemokine proteins that could cause an inflammatory reaction, and reversible mild to moderate inflammation in the lungs and liver. GDC-0917 had been in phase I clinical trials by Genentech, Inc. for the treatment of Refractory Solid Tumors or Lymphoma. The principal toxicities related to CUDC-427 were mild to moderate in severity and included fatigue, nausea, vomiting, and rash.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cIAP1/cIAP2 2 Target ID: CHEMBL3038465 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27076626	Antagonist 2849

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 147 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27076626	Primary		Phase I 438	Unknown Approved Use Unknown
Lymphoma 60 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27076626	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4.57 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24041744/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
957 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27076626	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
744 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27076626	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
37.1 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/24041744/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
7000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27076626	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5320 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27076626	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:	GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.98 h REVIEW https://pubmed.ncbi.nlm.nih.gov/24041744/	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
5.62 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27076626	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		GDC-0917 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
15% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24041744	unknown		GDC-0917 plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AC09	https://www.1pchem.com/search?query=1P00AC09
AbovChem LLC	HY-15835
BLD Pharm	BD630301	http://www.bldpharm.com/search/Search.html?keyword=BD630301
Chem Scene	CS-3392	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3392
ChemShuttle	140483	https://www.chemshuttle.com/catalogsearch/result/?q=140483
eMolecules	50283568	https://orderbb.emolecules.com/search/#?query=50283568
Hangzhou Yuhao Chemical Technology	YH65229
Lan Pharmatech	LQT-B42417
mcule	MCULE-6346127465	https://mcule.com/MCULE-6346127465/
MedChem Express	HY-15835	https://www.medchemexpress.com/search.html?q=HY-15835&ft=&fa=&fp=
MolPort	MolPort-046-417-101	https://www.molport.com/shop/molecule-link/MolPort-046-417-101
Norris Pharm	NSZB-A231238

PubMed

Title	Date	PubMed
A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors.	2016-09-15	27076626

Patents

Sample Use Guides

In Vivo Use Guide

CUDC-427 (GDC-0917) can be administered safely at doses up to 600 mg daily for 14 days every 3 weeks.

Route of Administration: Oral

In Vitro Use Guide

Whole blood was collected in eight 8-ml cell preparation tubes (Becton Dickinson, Franklin Lakes, NJ) containing sodium heparin from each donor. Blood was pooled and transferred to 14-ml tubes and incubated in the dark at room temperature for ;16 hours in the presence of the vehicle DMSO (dimethylsulfoxide) or 0.0001–10 mkM of GDC-0917. After incubation, each blood sample was transferred back into a cell preparation tube, and PBMCs were harvested from blood after centrifugation as per manufacturer’s instructions and washed in cold PBS. Next, resulting PBMC pellets were lysed in 100 ml 1 cell extraction buffer (Invitrogen, Grand Island, NY) containing protease inhibitors (Roche, Basel, Switzerland). Lysates were transferred to 1.5-ml microfuge tubes and centrifuged at 13,000g for 10 minutes at 4°C. The total cellular protein concentration for each PBMC lysate was determined using a microbicinchoninic acid assay (Pierce Biotechnology, Rockford, IL). The cIAP1 concentration was determined using an internally developed qualified cIAP1 immunoassay.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:54:17 GMT 2025` Edited by `admin` on `Mon Mar 31 20:54:17 GMT 2025`
Record UNII	KWH46ZDG32
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CUDC-427

Preferred Name

English

GDC-0917

Common Name

English

CUDC 427 [WHO-DD]

Common Name

English

L-PROLINAMIDE, N-METHYL-L-ALANYL-(2S)-2-CYCLOHEXYLGLYCYL-N-(2-(2-OXAZOLYL)-4-PHENYL-5-THIAZOLYL)-

Systematic Name

English

Code System Code Type Description

PUBCHEM

71600094