APITOLISIB

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H30N8O3S
Molecular Weight	498.601
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](O)C(=O)N1CCN(CC2=C(C)C3=C(S2)C(=NC(=N3)C4=CN=C(N)N=C4)N5CCOCC5)CC1

InChI

InChIKey=YOVVNQKCSKSHKT-HNNXBMFYSA-N

InChI=1S/C23H30N8O3S/c1-14-17(13-29-3-5-31(6-4-29)22(33)15(2)32)35-19-18(14)27-20(16-11-25-23(24)26-12-16)28-21(19)30-7-9-34-10-8-30/h11-12,15,32H,3-10,13H2,1-2H3,(H2,24,25,26)/t15-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H30N8O3S
Molecular Weight	498.601
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714
Curator's Comment: Description was created based on several sources, including http://www.pharmacodia.com/yaodu/html/v1/chemicals/1772c976b13a8c7b23be3976965dd543.html http://adisinsight.springer.com/drugs/800030889

Apitolisib, a dual inhibitor of mTOR and phosphatidylinositol 3-kinase (PI3K), was being developed by Roche and Genentech as an orally administered therapy of cancer. Apitolisib is a selective, potent, orally bioavailable inhibitor of Class I PI3 kinase (PI3K) and mTOR kinase (TORC1/2) with excellent pharmacokinetic and pharmaceutical properties. Apitolisib displayed excellent potency against class I PI3K isoforms (IC50 PI3K-α, β, δ and γ = 4.8, 27, 6.7 and 14 nM) and mTOR kinase (IC50 = 17 nM) and selectivity against a large panel of other kinases. Apitolisib is in phase II trials by Genentech for the treatment of breast cancer, prostate cancer, endometrium cancer, kidney cancer. However, no recent development has been reported. It is also in phase I trials by Genentech for the treatment of non-Hodgkin's lymphoma.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
PI3-kinase p110-alpha subunit 41 Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714	Inhibitor 8504	5.0 nM [IC50]
PI3-kinase p110-delta subunit 43 Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714	Inhibitor 8504	7.0 nM [IC50]
PI3-kinase p110-gamma subunit 32 Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714	Inhibitor 8504	14.0 nM [IC50]
PI3-kinase p110-beta subunit 31 Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714	Inhibitor 8504	27.0 nM [IC50]
Serine/threonine-protein kinase mTOR 35 Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714	Inhibitor 8504	17.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Endometrial cancer 44 Sources: https://clinicaltrials.gov/ct2/show/NCT01455493	Primary	Phase II 1147	Unknown Approved Use Unknown
Renal cell carcinoma 33 Sources: https://clinicaltrials.gov/ct2/show/NCT01442090	Primary	Phase II 1147	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://clinicaltrials.gov/ct2/show/NCT01437566	Primary	Phase II 1147	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT01485861	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
154.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26787751/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.1 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25165011	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1763 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26787751/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
108 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25165011	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26787751/	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25165011	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		APITOLISIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
42% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22696419			APITOLISIB plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111455	https://www.001chemical.com/chem/search?q=DY111455
1PlusChem LLC	1P0036G5	https://www.1pchem.com/search?query=1P0036G5
A2B Chem	AB47525	http://a2bchem.com/prod/AB47525
AChemBlock	L21799	http://www.achemblock.com/catalogsearch/result/?q=L21799
AK Scientific	X7458	https://aksci.com/item_detail.php?cat=X7458
Angene	AGN-PC-0WH9J3	http://www.angenechemical.com/productshow/AGN-PC-0WH9J3.html
AOBIOUS INC	AOB87742	http://aobious.com/aobious/search?search_query=AOB87742
ApexBio Technology	B2184	https://www.apexbt.com/catalogsearch/result/?q=B2184
AstaTech	42551	http://astatechinc.com/CPSResult.php?CRNO=42551
Axon MedChem	1782	https://www.axonmedchem.com/product/1782
BioSynth	J-502360	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-502360
BLD Pharm	BD305458	http://www.bldpharm.com/search/Search.html?keyword=BD305458
BOC Sciences	1032754-93-0	http://www.bocsci.com/description.asp?cas=1032754-93-0
Capot Chemical	24448	https://www.capotchem.com/search.do?q=24448
Cayman Chemical	18303	http://www.caymanchem.com/app/template/Product.vm/catalog/18303
Chem Scene	CS-0590	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0590
ChemShuttle	104804	https://www.chemshuttle.com/catalogsearch/result/?q=104804
eMolecules	108762410	https://orderbb.emolecules.com/search/#?query=108762410
eMolecules	300652060	https://orderbb.emolecules.com/search/#?query=300652060
eMolecules	42777436	https://orderbb.emolecules.com/search/#?query=42777436
eNovation Chemicals	D573205	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D573205&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A041	http://www.excenen.com/searchresultlist.php?id=EX-A041
KeyOrganics	AS-16289	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16289
Matrix Scientific	145204	http://www.matrixscientific.com/145204.html
mcule	MCULE-8352559558	https://mcule.com/MCULE-8352559558/
mcule	MCULE-9729346458	https://mcule.com/MCULE-9729346458/
MedChem Express	HY-13246	https://www.medchemexpress.com/search.html?q=HY-13246&ft=&fa=&fp=
Molcore	MC111455	http://www.molcore.com/CatMC111455.html
Molnova	M10158	https://www.molnova.com/en/serch-list.html?keywords=M10158
MolPort	MolPort-023-293-511	https://www.molport.com/shop/molecule-link/MolPort-023-293-511
MuseChem	I000195	https://www.musechem.com/product/I000195.html
Selleck Chemicals	S2696	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2696
ShangHai Biochempartner	BCP000437	http://www.biochempartner.com/search_BCP000437
ShangHai Biochempartner	BCP02622	http://www.biochempartner.com/search_BCP02622
TargetMol	T1916	https://www.targetmol.com/search?keyword=T1916
Tetrahedron	TS87933	http://www.thsci.com/search.do?q=TS87933
Wonderchem	WD09P15	http://www.wonder-chem.com/search.html?text=WD09P15

PubMed

Title	Date	PubMed
Screening hospital admissions from the emergency department for occult carbon monoxide poisoning.	1990 Jul	2094235
The phosphoinositide 3-kinase pathway.	2002 May 31	12040186
GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway.	2011 Dec	21998291
Phosphoinositide 3-kinase (PI3K) pathway alterations are associated with histologic subtypes and are predictive of sensitivity to PI3K inhibitors in lung cancer preclinical models.	2012 Dec 15	23136191
Preclinical assessment of the absorption and disposition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor GDC-0980 and prediction of its pharmacokinetics and efficacy in human.	2012 Sep	22696419

Patents

Sample Use Guides

In Vivo Use Guide

administered orally at a 40 mg daily dose

Route of Administration: Oral

In Vitro Use Guide

In vitro, Apitolisib significantly inhibits cell proliferation in PC3 and MCF7 cells with IC50 of 307 nM and 255 nM, respectively.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:03:14 GMT 2025` Edited by `admin` on `Mon Mar 31 21:03:14 GMT 2025`
Record UNII	1C854K1MIJ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

APITOLISIB

Official Name

English

G-038390

Preferred Name

English

GNE-390

Common Name

English

apitolisib [INN]

Common Name

English

Apitolisib [WHO-DD]

Common Name

English

APITOLISIB [USAN]

Common Name

English

(S)-1-(4-((2-(2-AMINOPYRIMIDIN-5-YL)-7-METHYL-4-(MORPHOLIN-4-YL)THIENO(3,2-D)PYRIMIDIN-6-YL)METHYL)PIPERAZIN-1-YL)-2-HYDROXYPROPAN-1-ONE

Systematic Name

English

RG-7422

Code

English

(2S)-1-(4-((2-(2-AMINOPYRIMIDIN-5-YL)-7-METHYL-4-(MORPHOLIN-4-YL)THIENO(3,2-D)PYRIMIDIN-6-YL)METHYL(PIPERAZIN-1-YL)-2-HYDROXYPROPAN-1-ONE

Common Name

English

RG7422

Code

English

1-PROPANONE, 1-(4-((2-(2-AMINO-5-PYRIMIDINYL)-7-METHYL-4-(4-MORPHOLINYL)THIENO(3,2-D)PYRIMIDIN-6-YL)METHYL)-1-PIPERAZINYL)-2-HYDROXY-, (2S)-

Systematic Name

English

GDC-0980.1

Code

English

GDC-0980

Code

English

G-038390.1

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1404