GDC-0152

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H34N6O3S
Molecular Weight	498.641
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=NS3)C4=CC=CC=C4

InChI

InChIKey=WZRFLSDVFPIXOV-LRQRDZAKSA-N

InChI=1S/C25H34N6O3S/c1-16(26-2)22(32)27-21(18-12-7-4-8-13-18)25(34)31-15-9-14-19(31)23(33)28-24-20(29-30-35-24)17-10-5-3-6-11-17/h3,5-6,10-11,16,18-19,21,26H,4,7-9,12-15H2,1-2H3,(H,27,32)(H,28,33)/t16-,19-,21-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H34N6O3S
Molecular Weight	498.641
Charge	0
Count

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

Description
Sources: http://adisinsight.springer.com/drugs/800022402
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22413863 | https://www.ncbi.nlm.nih.gov/pubmed/27490930

GDC-0152 binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2. GDC-0152 promotes degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells. GDC-0152 improves outcome in breast cancer and glioma xenografted mouse. GDC 0512 was in phase I development in the US for the treatment of cancer; however, Roche announced in their 2009 results presentation, that development of the agent has been discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Inhibitor of apoptosis protein 3 6 Target ID: CHEMBL4198 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22413863	Antagonist 2849	28.0 nM [Ki]
Baculoviral IAP repeat-containing protein 7 1 Target ID: CHEMBL1075127 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22413863	Antagonist 2849	14.0 nM [Ki]
Baculoviral IAP repeat-containing protein 2 9 Target ID: CHEMBL5462 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22413863	Antagonist 2849	17.0 nM [Ki]
Baculoviral IAP repeat-containing protein 3 9 Target ID: CHEMBL5335 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22413863	Antagonist 2849	43.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: http://adisinsight.springer.com/drugs/800022402	Primary		Phase I 438	Unknown Approved Use Unknown
Glioblastoma multiforme 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27490930	Primary		Basic research	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
3400 ng × h/mL EXPERIMENT https://doi.org/10.1016/S1359-6349(10)72100-5	1.48 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.48 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GDC-0152 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2580 ng × h/mL EXPERIMENT https://doi.org/10.1016/S1359-6349(10)72100-5	1.06 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.06 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GDC-0152 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4 h EXPERIMENT https://doi.org/10.1016/S1359-6349(10)72100-5	1.48 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.48 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GDC-0152 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4 h EXPERIMENT https://doi.org/10.1016/S1359-6349(10)72100-5	1.06 mg/kg 1 times / 2 weeks multiple, intravenous dose: 1.06 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		GDC-0152 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
ApexBio Technology	A4224	https://www.apexbt.com/catalogsearch/result/?q=A4224
BLD Pharm	BD630944	http://www.bldpharm.com/search/Search.html?keyword=BD630944
Cayman Chemical	17810	http://www.caymanchem.com/app/template/Product.vm/catalog/17810
Chem Scene	CS-3546	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3546
ChemShuttle	141844	https://www.chemshuttle.com/catalogsearch/result/?q=141844
eMolecules	222565590	https://orderbb.emolecules.com/search/#?query=222565590
eMolecules	260479657	https://orderbb.emolecules.com/search/#?query=260479657
eMolecules	49383421	https://orderbb.emolecules.com/search/#?query=49383421
Excenen	EX-A1658	http://www.excenen.com/searchresultlist.php?id=EX-A1658
mcule	MCULE-6443999185	https://mcule.com/MCULE-6443999185/
mcule	MCULE-8371197728	https://mcule.com/MCULE-8371197728/
MedChem Express	HY-13638	https://www.medchemexpress.com/search.html?q=HY-13638&ft=&fa=&fp=
Molnova	M16352	https://www.molnova.com/en/serch-list.html?keywords=M16352
MolPort	MolPort-035-395-791	https://www.molport.com/shop/molecule-link/MolPort-035-395-791
Selleck Chemicals	S7010	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7010
TargetMol	T6299	https://www.targetmol.com/search?keyword=T6299

PubMed

Title	Date	PubMed
Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152.	2016-08-04	27490930
IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα.	2016-06-07	27129149
Discovery of Novel, Potent, and Specific Cell-Death Inducers in the Jurkat Acute Lymphoblastic Leukemia Cell Line.	2015-10	26267799
GDC-0152 attenuates the malignant progression of osteosarcoma promoted by ANGPTL2 via PI3K/AKT but not p38MAPK signaling pathway.	2015-04	25651778
GDC-0152 induces apoptosis through down-regulation of IAPs in human leukemia cells and inhibition of PI3K/Akt signaling pathway.	2015-02	25273171
Evaluation of metabolism and disposition of GDC-0152 in rats using 14C labeling strategy at two different positions: a novel formation of hippuric acid from 4-phenyl-5-amino-1,2,3-thiadiazole.	2013-02	23223496
Toxicity profile of small-molecule IAP antagonist GDC-0152 is linked to TNF-α pharmacology.	2013-01	22956632
Validation and application of a liquid chromatography-tandem mass spectrometric method for the determination of GDC-0152 in human plasma using solid-phase extraction.	2013-01	22623056
Dogs are more sensitive to antagonists of inhibitor of apoptosis proteins than rats and humans: a translational toxicokinetic/toxicodynamic analysis.	2012-11	22843607
Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152).	2012-05-10	22413863

Patents

Sample Use Guides

In Vivo Use Guide

Oral dosing once weekly with 10, 50, or 100 mg/kg resulted in significant tumor volume reduction in human-tumor xenograft mouse models of MDA-MB-231 breast cancer. Similar results were obtained when dosed at 10 mg/kg daily or every third day for three weeks. In humans, GDC-0152 exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. 10 and 20 mg/kg of GDC-0152 (intravenous omce a week) treatment improved xenografted mice survival and slowed down glioblastoma tumor growth.

Route of Administration: Other

In Vitro Use Guide

0.01 - 100 μM GDC-0152 affected glioma cell viability in time- and dose-dependent manner.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:17:03 GMT 2025` Edited by `admin` on `Mon Mar 31 18:17:03 GMT 2025`
Record UNII	4KW1M48SHS
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

L-PROLINAMIDE, N-METHYL-L-ALANYL-(2S)-2-CYCLOHEXYLGLYCYL-N-(4-PHENYL-1,2,3-THIADIAZOL-5-YL)-

Preferred Name

English

GDC-0152

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID00236307