TASELISIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H28N8O2
Molecular Weight	460.5315
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N1N=C(C)N=C1C2=CN3CCOC4=CC(=CC=C4C3=N2)C5=CN(N=C5)C(C)(C)C(N)=O

InChI

InChIKey=BEUQXVWXFDOSAQ-UHFFFAOYSA-N

InChI=1S/C24H28N8O2/c1-14(2)32-22(27-15(3)29-32)19-13-30-8-9-34-20-10-16(6-7-18(20)21(30)28-19)17-11-26-31(12-17)24(4,5)23(25)33/h6-7,10-14H,8-9H2,1-5H3,(H2,25,33)

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800033797
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23662903 | https://www.ncbi.nlm.nih.gov/pubmed/25172762 | https://www.biooncology.com/pipeline-molecules/taselisib.html

Taselisib (GDC-0032) is an highly selective small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K) p110-α isoform (PIK3CA). Taselisib is designed to bind to the ATP-binding pocket of PIK3CA to potentially prevent subsequent downstream signaling. Taselisib caused a strong differential growth inhibition in carcinoma cells harbored oncogenic PIK3CA mutations. In preclinical studies, taselisib induced growth inhibition in PIK3CA-mutant xenograft mouse models. Genentech (a Roche subsidiary) is developing taselib primarily for the treatment of solid tumours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23662903	Inhibitor 8297		0.29 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800033797	Primary	Phase III 656	Unknown Approved Use Unknown
Squamous cell lung cancer 2 Sources: http://adisinsight.springer.com/drugs/800033797	Primary	Phase III 656	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 79 Sources: http://adisinsight.springer.com/drugs/800033797	Primary	Phase II 1132	Unknown Approved Use Unknown
Uterine cancer 3 Sources: http://adisinsight.springer.com/drugs/800033797	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800033797	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.091 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
0.111 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.188 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	8 mg 1 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.302 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	12 mg 1 times / day steady-state, oral dose: 12 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.441 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	16 mg 1 times / day steady-state, oral dose: 16 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1.49 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FASTED
1.79 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	3 mg 1 times / day steady-state, oral dose: 3 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.21 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	8 mg 1 times / day steady-state, oral dose: 8 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.1 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	12 mg 1 times / day steady-state, oral dose: 12 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8.1 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28331003/	16 mg 1 times / day steady-state, oral dose: 16 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TASELISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111482	https://www.001chemical.com/chem/search?q=DY111482
1PlusChem LLC	1P000YD6	https://www.1pchem.com/search?query=1P000YD6
A2B Chem	AA43738	http://a2bchem.com/prod/AA43738
AChemBlock	P50900	http://www.achemblock.com/catalogsearch/result/?q=P50900
AK Scientific	9344AF	https://aksci.com/item_detail.php?cat=9344AF
Angene	AGN-PC-0WH9JQ	http://www.angenechemical.com/productshow/AGN-PC-0WH9JQ.html
ApexBio Technology	B1047	https://www.apexbt.com/catalogsearch/result/?q=B1047
AstaTech	42575	http://astatechinc.com/CPSResult.php?CRNO=42575
Axon MedChem	2927	https://www.axonmedchem.com/product/2927
BLD Pharm	BD450324	http://www.bldpharm.com/search/Search.html?keyword=BD450324
BOC Sciences	1282512-48-4	http://www.bocsci.com/description.asp?cas=1282512-48-4
Cayman Chemical	17387	http://www.caymanchem.com/app/template/Product.vm/catalog/17387
Chem Scene	CS-1817	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1817
ChemShuttle	105144	https://www.chemshuttle.com/catalogsearch/result/?q=105144
Excenen	EX-A1581	http://www.excenen.com/searchresultlist.php?id=EX-A1581
Hairui	TAJB019	http://www.hairuichem.com/en/product/search.do?q=TAJB019
KeyOrganics	AS-10662	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-10662
Matrix Scientific	145388	http://www.matrixscientific.com/145388.html
MedChem Express	HY-13898	https://www.medchemexpress.com/search.html?q=HY-13898&ft=&fa=&fp=
MolPort	MolPort-039-062-173	https://www.molport.com/shop/molecule-link/MolPort-039-062-173
Molcore	MC111482	http://www.molcore.com/CatMC111482.html
Molnova	M11159	https://www.molnova.com/en/serch-list.html?keywords=M11159
MuseChem	I001112	https://www.musechem.com/product/I001112.html
Selleck Chemicals	S7103	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7103
ShangHai Biochempartner	BCP001087	http://www.biochempartner.com/search_BCP001087
ShangHai Biochempartner	BCP09253	http://www.biochempartner.com/search_BCP09253
TargetMol	T1999	https://www.targetmol.com/search?keyword=T1999
Toronto Research Chemicals	D439130	https://www.trc-canada.com/product-detail/?CatNum=D439130
Toronto Research Chemicals	D446475	https://www.trc-canada.com/product-detail/?CatNum=D446475
eMolecules	48670995	https://orderbb.emolecules.com/search/#?query=48670995
mcule	MCULE-9997946172	https://mcule.com/MCULE-9997946172/

PubMed

Title	Date	PubMed
Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity.	2013 Jun 13	23662903
Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo.	2014 Nov	25172762
Taselisib (GDC-0032), a Potent β-Sparing Small Molecule Inhibitor of PI3K, Radiosensitizes Head and Neck Squamous Carcinomas Containing Activating PIK3CA Alterations.	2016 Apr 15	26589432

Patents

Sample Use Guides

In Vivo Use Guide

A Phase Ib dose escalation study evaluating taselisib doses ranging from 6-9 mg QD capsules

Route of Administration: Oral

In Vitro Use Guide

treatment with 50 nM, 100 nM and 500 nM of taselisib for 24 hrs was able to significantly increase the fraction of cells in the G0/G1 cell cycle phase in the uterine serous carcinoma cell lines when compared with the untreated controls

Name

Type

Language

TASELISIB

Official Name

English

TASELISIB [USAN]

Common Name

English

taselisib [INN]

Common Name

English

2-(4-(2-(1-ISOPROPYL-3-METHYL-1H-1,2,4-TRIAZOL-5-YL)-5,6-DIHYDROBENZO(F)IMIDAZO(1,2-D)(1,4)OXAZEPIN-9-YL)-1H-PYRAZOL-1-YL)-2-METHYLPROPANAMIDE

Systematic Name

English

Taselisib [WHO-DD]

Common Name

English

GDC-0032

Code

English

1H-PYRAZOLE-1-ACETAMIDE, 4-(5,6-DIHYDRO-2-(3-METHYL-1-(1-METHYLETHYL)-1H-1,2,4-TRIAZOL-5-YL)IMIDAZO(1,2-D)(1,4)BENZOXAZEPIN-9-YL)-.ALPHA.,.ALPHA.-DIMETHYL-

Systematic Name

English

RG-7604

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825