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
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
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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21981714Curator'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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4005 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714 |
5.0 nM [IC50] | ||
Target ID: CHEMBL3130 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714 |
7.0 nM [IC50] | ||
Target ID: CHEMBL3267 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714 |
14.0 nM [IC50] | ||
Target ID: CHEMBL3145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714 |
27.0 nM [IC50] | ||
Target ID: CHEMBL2842 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714 |
17.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Screening hospital admissions from the emergency department for occult carbon monoxide poisoning. | 1990 Jul |
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The phosphoinositide 3-kinase pathway. | 2002 May 31 |
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Defining the role of mTOR in cancer. | 2007 Jul |
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mTOR signaling at a glance. | 2009 Oct 15 |
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The emerging mechanisms of isoform-specific PI3K signalling. | 2010 May |
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GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. | 2011 Dec |
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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 |
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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 |
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Modulation of Akt/mTOR signaling overcomes sunitinib resistance in renal and prostate cancer cells. | 2012 Jul |
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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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01442090
administered orally at a 40 mg daily dose
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21981714
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
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Fri Jun 25 23:20:49 UTC 2021
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1C854K1MIJ
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C129825
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DB12180
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SUB126157
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1C854K1MIJ
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ACTIVE MOIETY |
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Biological Half-life | PHARMACOKINETIC |
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