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MedKoo Cat#: 205470 | Name: GDC-0980 (Apitolisib)
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Apitolisib, also known as GDC-0980 and RG7422; or GNE390, is a dual PI3 kinase/mTOR inhibitor, is also a n orally available agent targeting phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor GDC-0980 inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR.

Chemical Structure

GDC-0980 (Apitolisib)
GDC-0980 (Apitolisib)
CAS#1032754-93-0

Theoretical Analysis

MedKoo Cat#: 205470

Name: GDC-0980 (Apitolisib)

CAS#: 1032754-93-0

Chemical Formula: C23H30N8O3S

Exact Mass: 498.2162

Molecular Weight: 498.60

Elemental Analysis: C, 55.40; H, 6.06; N, 22.47; O, 9.63; S, 6.43

Price and Availability

Size Price Availability Quantity
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 850.00 Ready to ship
500mg USD 1,850.00 Ready to ship
1g USD 2,950.00 Ready to ship
2g USD 5,350.00 Ready to ship
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Related CAS #
No Data
Synonym
GDC0980; GDC-0980; GDC 0980; RG7422; RG-7422; RG 7422; GNE 390; GNE-390; GNE390; Apitolisib
IUPAC/Chemical Name
(S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one.
InChi Key
YOVVNQKCSKSHKT-HNNXBMFYSA-N
InChi Code
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
SMILES Code
C[C@H](O)C(N1CCN(CC2=C(C)C3=NC(C4=CN=C(N)N=C4)=NC(N5CCOCC5)=C3S2)CC1)=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
GCD-0980 is potent across PI3K class I isoforms with IC(50)s of 5, 27, 7, and 14 nM for PI3Kα, β, δ, and γ, respectively, inhibits mTOR with a K(i) of 17 nM yet is highly selective versus a large panel of kinases including others in the PIKK family. On the basis of the cell potency, low clearance in mouse, and high free fraction, 2 demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer. [source: J Med Chem. 2011 Nov 10;54(21):7579-87.]      
Biological target:
Apitolisib (GDC-0980; GNE 390; RG 7422) is a Class I PI3 kinase and mTOR kinase (TORC1/2) inhibitor with IC50s of 5 nM/27 nM/7 nM/14 nM for PI3Kα/PI3Kβ/PI3Kδ/PI3Kγ, and with a Ki of 17 nM for mTOR.
In vitro activity:
GDC-0980 is a potent small-molecule inhibitor of class I PI3K isoforms and mTOR kinase and displays excellent selectivity against a large panel of other kinases, including closely related family members DNA-PK, VPS34, c2alpha, and c2beta (Fig. 1; ref. 19). This study assessed a panel of breast, non-small cell lung, colon, pancreatic, melanoma, and prostate cancer cell lines in cell viability experiments to profile the activity of GDC-0980 in vitro (Fig. 1). GDC-0980 was most effective in prostate (IC50 < 200 nmol/L 50%), <500 nmol/L 100%), breast (IC50 <200 nmol/L 37%, <500 nmol/L 78%) and NSCLC lines (IC50 <200 nmol/L 29%, <500 nmol/L0 88%), and was less effective in pancreatic (IC50 <200 nmol/L 13%, <500 nmol/L 67%) and melanoma cell lines (IC50 <200 nmol/L 0%, <500 nmol/L 33%). Taken together, GDC-0980 had broad cellular activity with potency below 500 nmol/L in 124 out of the 167 cell lines tested. Reference: Mol Cancer Ther. 2011 Dec;10(12):2426-36. https://pubmed.ncbi.nlm.nih.gov/21998291/
In vivo activity:
GDC-0980 was administered orally, daily, to MCF7-neo/HER2 tumor-bearing mice at doses ranging from 0.25 to 7.5 mg/kg. Tumor growth inhibition results are presented in Fig. 7C. The inhibition of the MCF7-neo/HER2 tumor growth appeared to be dose dependent. An indirect response model was fitted to the tumor data from all of the doses (eq. 1) and appeared to describe them adequately. The comparison between the observed TVs and the model predictions is presented in Fig. 7D. The estimates of the pharmacodynamic parameters describing MCF7-neo/HER2 tumor growth and reduction effect by GDC-0980 are presented in Table 8. Reference: Drug Metab Dispos. 2012 Sep;40(9):1785-96. https://pubmed.ncbi.nlm.nih.gov/22696419/
Solvent mg/mL mM
Solubility
DMSO 19.8 39.63
DMSO:PBS (pH 7.2) (1:5) 0.2 0.30
DMF 25.0 50.14
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 498.60 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, Lesnick JD, Lewis C, Nonomiya J, Pang J, Salphati L, Olivero AG, Sutherlin DP, O'Brien C, Spoerke JM, Patel S, Lensun L, Kassees R, Ross L, Lackner MR, Sampath D, Belvin M, Friedman LS. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13. PMID: 21998291. 2. Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J, Heffron T, Lesnick J, Lewis C, Mathieu S, Murray J, Nonomiya J, Pang J, Pegg N, Prior WW, Rouge L, Salphati L, Sampath D, Tian Q, Tsui V, Wan NC, Wang S, Wei B, Wiesmann C, Wu P, Zhu BY, Olivero A. 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. J Med Chem. 2011 Nov 10;54(21):7579-87. doi: 10.1021/jm2009327. Epub 2011 Oct 7. PMID: 21981714. 3. Salphati L, Pang J, Plise EG, Lee LB, Olivero AG, Prior WW, Sampath D, Wong S, Zhang X. 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. Drug Metab Dispos. 2012 Sep;40(9):1785-96. doi: 10.1124/dmd.112.046052. Epub 2012 Jun 13. PMID: 22696419. 4. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, Lesnick JD, Lewis C, Nonomiya J, Pang J, Salphati L, Olivero AG, Sutherlin DP, O'Brien C, Spoerke JM, Patel S, Lensun L, Kassees R, Ross L, Lackner MR, Sampath D, Belvin M, Friedman LS. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13. PMID: 21998291.
In vitro protocol:
1. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, Lesnick JD, Lewis C, Nonomiya J, Pang J, Salphati L, Olivero AG, Sutherlin DP, O'Brien C, Spoerke JM, Patel S, Lensun L, Kassees R, Ross L, Lackner MR, Sampath D, Belvin M, Friedman LS. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13. PMID: 21998291. 2. Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J, Heffron T, Lesnick J, Lewis C, Mathieu S, Murray J, Nonomiya J, Pang J, Pegg N, Prior WW, Rouge L, Salphati L, Sampath D, Tian Q, Tsui V, Wan NC, Wang S, Wei B, Wiesmann C, Wu P, Zhu BY, Olivero A. 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. J Med Chem. 2011 Nov 10;54(21):7579-87. doi: 10.1021/jm2009327. Epub 2011 Oct 7. PMID: 21981714.
In vivo protocol:
1. Salphati L, Pang J, Plise EG, Lee LB, Olivero AG, Prior WW, Sampath D, Wong S, Zhang X. 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. Drug Metab Dispos. 2012 Sep;40(9):1785-96. doi: 10.1124/dmd.112.046052. Epub 2012 Jun 13. PMID: 22696419. 2. Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, Lesnick JD, Lewis C, Nonomiya J, Pang J, Salphati L, Olivero AG, Sutherlin DP, O'Brien C, Spoerke JM, Patel S, Lensun L, Kassees R, Ross L, Lackner MR, Sampath D, Belvin M, Friedman LS. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13. PMID: 21998291.
1: English DP, Bellone S, Cocco E, Bortolomai I, Pecorelli S, Lopez S, Silasi DA, Schwartz PE, Rutherford T, Santin AD. Oncogenic PIK3CA gene mutations and HER2/neu gene amplifications determine the sensitivity of uterine serous carcinoma cell lines to GDC-0980, a selective inhibitor of Class I PI3 kinase and mTOR kinase (TORC1/2). Am J Obstet Gynecol. 2013 Nov;209(5):465.e1-9. doi: 10.1016/j.ajog.2013.07.020. Epub 2013 Jul 24. PubMed PMID: 23891627. 2: Salphati L, Pang J, Plise EG, Lee LB, Olivero AG, Prior WW, Sampath D, Wong S, Zhang X. 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. Drug Metab Dispos. 2012 Sep;40(9):1785-96. doi: 10.1124/dmd.112.046052. Epub 2012 Jun 13. PubMed PMID: 22696419. 3: Wallin JJ, Edgar KA, Guan J, Berry M, Prior WW, Lee L, Lesnick JD, Lewis C, Nonomiya J, Pang J, Salphati L, Olivero AG, Sutherlin DP, O'Brien C, Spoerke JM, Patel S, Lensun L, Kassees R, Ross L, Lackner MR, Sampath D, Belvin M, Friedman LS. GDC-0980 is a novel class I PI3K/mTOR kinase inhibitor with robust activity in cancer models driven by the PI3K pathway. Mol Cancer Ther. 2011 Dec;10(12):2426-36. doi: 10.1158/1535-7163.MCT-11-0446. Epub 2011 Oct 13. PubMed PMID: 21998291. 4: Sutherlin DP, Bao L, Berry M, Castanedo G, Chuckowree I, Dotson J, Folks A, Friedman L, Goldsmith R, Gunzner J, Heffron T, Lesnick J, Lewis C, Mathieu S, Murray J, Nonomiya J, Pang J, Pegg N, Prior WW, Rouge L, Salphati L, Sampath D, Tian Q, Tsui V, Wan NC, Wang S, Wei B, Wiesmann C, Wu P, Zhu BY, Olivero A. 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. J Med Chem. 2011 Nov 10;54(21):7579-87. doi: 10.1021/jm2009327. Epub 2011 Oct 7. PubMed PMID: 21981714.