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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H30N8O3S
Molecular Weight 498.6031
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APITOLISIB

SMILES

Cc1c(CN2CCN(CC2)C(=O)[C@]([H])(C)O)sc3c1nc(-c4c[nH]c(=N)nc4)nc3N5CCOCC5

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 498.6031
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Screening hospital admissions from the emergency department for occult carbon monoxide poisoning.
1990 Jul
The phosphoinositide 3-kinase pathway.
2002 May 31
Defining the role of mTOR in cancer.
2007 Jul
mTOR signaling at a glance.
2009 Oct 15
The emerging mechanisms of isoform-specific PI3K signalling.
2010 May
GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway.
2011 Dec
Discovery of a potent, selective, and orally available class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) kinase inhibitor (GDC-0980) for the treatment of cancer.
2011 Nov 10
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
Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells.
2012 Jul
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
Patents

Sample Use Guides

administered orally at a 40 mg daily dose
Route of Administration: Oral
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 Fri Jun 25 23:20:49 UTC 2021
Edited
by admin
on Fri Jun 25 23:20:49 UTC 2021
Record UNII
1C854K1MIJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APITOLISIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
APITOLISIB [WHO-DD]
Common Name English
GNE-390
Common Name English
APITOLISIB [INN]
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
G-038390
Code English
GDC-0980
Code English
G-038390.1
Code English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
Code System Code Type Description
INN
9644
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
CAS
1032754-93-0
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
DRUG BANK
DB12180
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
NCI_THESAURUS
C91731
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
CAS
1309384-87-9
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
SUPERSEDED
PUBCHEM
25254071
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
EVMPD
SUB126157
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
EPA CompTox
1032754-93-0
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL1922094
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
FDA UNII
1C854K1MIJ
Created by admin on Fri Jun 25 23:20:49 UTC 2021 , Edited by admin on Fri Jun 25 23:20:49 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC ORAL ADMINISTRATION

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