GDC-0941 (Pictilisib)
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MedKoo CAT#: 201395

CAS#: 957054-30-7 (free base)

Description: Pictilisib, also known as Pictrelisib, GDC-0941, RG7321 and GNE0941 , is an orally bioavailable, and is a potent small-molecule thieno[3,2-d]pyrimidine inhibitor of the class I phosphatidylinositol 3 kinase (PI3K) isoforms p100alpha and p100delta with potential antineoplastic activity. PI3K inhibitor GDC-0941 selectively binds to PI3K isoforms in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway; inhibition of tumor cell growth, motility and survival in susceptible tumor cell populations may result.


Chemical Structure

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GDC-0941 (Pictilisib)
CAS# 957054-30-7 (free base)

Theoretical Analysis

MedKoo Cat#: 201395
Name: GDC-0941 (Pictilisib)
CAS#: 957054-30-7 (free base)
Chemical Formula: C23H27N7O3S2
Exact Mass: 513.16168
Molecular Weight: 513.63
Elemental Analysis: C, 53.78; H, 5.30; N, 19.09; O, 9.34; S, 12.49

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Ready to ship
25.0mg USD 250.0 Ready to ship
50.0mg USD 450.0 Ready to ship
100.0mg USD 750.0 Ready to ship
200.0mg USD 1350.0 Ready to ship
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Related CAS #: 957054-30-7 (free base)   957054-33-0 (mesylate)  

Synonym: GDC-0941; GDC 0941; GDC0941; RG7321; RG-7321; RG 7321; GNE0941; GNE-0941; GNE 0941; Pictrelisib; Pictilisib

IUPAC/Chemical Name: 4-(2-(1H-indazol-4-yl)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine

InChi Key: LHNIIDJUOCFXAP-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H27N7O3S2/c1-35(31,32)30-7-5-28(6-8-30)15-16-13-20-21(34-16)23(29-9-11-33-12-10-29)26-22(25-20)17-3-2-4-19-18(17)14-24-27-19/h2-4,13-14H,5-12,15H2,1H3,(H,24,27)

SMILES Code: O=S(N1CCN(CC2=CC3=NC(C4=CC=CC5=C4C=NN5)=NC(N6CCOCC6)=C3S2)CC1)(C)=O

Appearance: White to off-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

Biological target: Pictilisib (GDC-0941) is a potent inhibitor of PI3Kα/δ with an IC50 of 3 nM, with modest selectivity against p110β (11-fold) and p110γ (25-fold).
In vitro activity: The effects of the clinically relevant inhibitor GDC-0941 on pathway regulation was evaluated. Initial studies were undertaken using adenovirus-based luciferase reporter assays to evaluate the effects of GDC-0941 on HIF activity in the thyroid carcinoma cell panel. GDC-0941 at 1 μM significantly inhibited HIF-driven reporter gene expression in air, 1% O2 (hypoxia), and anoxia (Supplemental Fig. 1). Effects on protein expression were then assessed in FTC133 and 8505c cells, which have hyperactivated PI3K. Cells were exposed to GDC-0941 under varying O2 tensions and lysates Western blotted. GDC-0941 reduced PI3K pathway activity in both cell lines, illustrated by decreased pAKT. Expression of HIF-1α and the downstream target CA-9 were also reduced. Down-regulation of the HIF target lactate dehydrogenase A (LDH-A) was observed only in FTC133 cells, and reduction in glucose transporter 1 (GLUT-1) was more pronounced in 8505c rather than FTC133 cells (Fig. 1A). Reference: J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2011-1426
In vivo activity: During treatment 1, the tumours in the GDC-0941-treated mice showed a marked non-linear shrinkage, with an average tumour regression of 52±8%. This tumour regression profile had been observed previously, with shrinkage reaching a plateaus after a month (24). When the GDC-0941 treatment ceased, the tumours in the test cohort mice grew again (off-treatment period 1) with an average linear tumour growth rate of 31.3±9.9 mm3/week (R2) (R2=0.98). R2 for individual GDC-0941 test mice are shown in Table II. After 21 days, the tumours had nearly returned to their size at the start of treatment. They grew on average nearly twice (1.9) as fast as before treatment (R2>R1); the difference was statistically significant (p=0.042). As with many molecular-targeted anticancer therapies, GDC-0941 stopped cells’ proliferation but was not completely cytocidal. Reference: Anticancer Res. 2012 Feb;32(2):415-20. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22287727/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 194.69

Preparing Stock Solutions

The following data is based on the product molecular weight 513.63 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
In vitro protocol: 1. Burrows N, Babur M, Resch J, Ridsdale S, Mejin M, Rowling EJ, Brabant G, Williams KJ. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12. PMID: 21994956. 2. Zou ZQ, Zhang LN, Wang F, Bellenger J, Shen YZ, Zhang XH. The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16. PMID: 22101421.
In vivo protocol: 1. Wullschleger S, García-Martínez JM, Duce SL. Quantitative MRI establishes the efficacy of PI3K inhibitor (GDC-0941) multi-treatments in PTEN-deficient mice lymphoma. Anticancer Res. 2012 Feb;32(2):415-20. PMID: 22287727; PMCID: PMC3292793. 2. Burrows N, Babur M, Resch J, Ridsdale S, Mejin M, Rowling EJ, Brabant G, Williams KJ. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways. J Clin Endocrinol Metab. 2011 Dec;96(12):E1934-43. doi: 10.1210/jc.2011-1426. Epub 2011 Oct 12. PMID: 21994956.

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1: De Wolf E, De Wolf C, Richardson A. ABT-737 and pictilisib synergistically enhance pitavastatin-induced apoptosis in ovarian cancer cells. Oncol Lett. 2018 Feb;15(2):1979-1984. doi: 10.3892/ol.2017.7516. Epub 2017 Dec 5. PubMed PMID: 29434898; PubMed Central PMCID: PMC5778268.

2: Keegan NM, Gleeson JP, Hennessy BT, Morris PG. PI3K inhibition to overcome endocrine resistance in breast cancer. Expert Opin Investig Drugs. 2018 Jan;27(1):1-15. doi: 10.1080/13543784.2018.1417384. Epub 2018 Jan 6. Review. PubMed PMID: 29252036.

3: Langhans J, Schneele L, Trenkler N, von Bandemer H, Nonnenmacher L, Karpel-Massler G, Siegelin MD, Zhou S, Halatsch ME, Debatin KM, Westhoff MA. The effects of PI3K-mediated signalling on glioblastoma cell behaviour. Oncogenesis. 2017 Nov 29;6(11):398. doi: 10.1038/s41389-017-0004-8. PubMed PMID: 29184057.

4: Yang W, Hosford SR, Traphagen NA, Shee K, Demidenko E, Liu S, Miller TW. Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer. FASEB J. 2018 Jan 3:fj201700477R. doi: 10.1096/fj.201700477R. [Epub ahead of print] PubMed PMID: 29127189.

5: Soria JC, Adjei AA, Bahleda R, Besse B, Ferte C, Planchard D, Zhou J, Ware J, Morrissey K, Shankar G, Lin W, Schutzman JL, Dy GK, Groen HJM. A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-small cell lung cancer. Eur J Cancer. 2017 Nov;86:186-196. doi: 10.1016/j.ejca.2017.08.027. Epub 2017 Oct 6. PubMed PMID: 28992562.

6: Suh KJ, Sung JH, Kim JW, Han SH, Lee HS, Min A, Kang MH, Kim JE, Kim JW, Kim SH, Lee JO, Kim YJ, Lee KW, Kim JH, Bang SM, Im SA, Lee JS. EGFR or HER2 inhibition modulates the tumor microenvironment by suppression of PD-L1 and cytokines release. Oncotarget. 2017 Jul 12;8(38):63901-63910. doi: 10.18632/oncotarget.19194. eCollection 2017 Sep 8. PubMed PMID: 28969039; PubMed Central PMCID: PMC5609971.

7: Chen J, Guo J, Cui X, Dai Y, Tang Z, Qu J, Raj JU, Hu Q, Gou D. The Long Noncoding RNA LnRPT Is Regulated by PDGF-BB and Modulates the Proliferation of Pulmonary Artery Smooth Muscle Cells. Am J Respir Cell Mol Biol. 2018 Feb;58(2):181-193. doi: 10.1165/rcmb.2017-0111OC. PubMed PMID: 28915060.

8: Zeng SX, Zhu Y, Ma AH, Yu W, Zhang H, Lin TY, Shi W, Tepper CG, Henderson PT, Airhart S, Guo JM, Xu CL, deVere White RW, Pan CX. The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer. Clin Cancer Res. 2017 Nov 1;23(21):6580-6591. doi: 10.1158/1078-0432.CCR-17-0033. Epub 2017 Aug 14. PubMed PMID: 28808038; PubMed Central PMCID: PMC5668181.

9: Leong S, Moss RA, Bowles DW, Ware JA, Zhou J, Spoerke JM, Lackner MR, Shankar G, Schutzman JL, van der Noll R, Voest EE, Schellens JHM. A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Pictilisib in Combination with Erlotinib in Patients with Advanced Solid Tumors. Oncologist. 2017 Dec;22(12):1491-1499. doi: 10.1634/theoncologist.2017-0090. Epub 2017 Aug 10. PubMed PMID: 28798270; PubMed Central PMCID: PMC5728021.

10: Lu T, Fraczkiewicz G, Salphati L, Budha N, Dalziel G, Smelick GS, Morrissey KM, Davis JD, Jin JY, Ware JA. Combining "Bottom-up" and "Top-down" Approaches to Assess the Impact of Food and Gastric pH on Pictilisib (GDC-0941) Pharmacokinetics. CPT Pharmacometrics Syst Pharmacol. 2017 Nov;6(11):747-755. doi: 10.1002/psp4.12228. Epub 2017 Oct 17. PubMed PMID: 28748626; PubMed Central PMCID: PMC5702897.

11: Nathan MR, Schmid P. A Review of Fulvestrant in Breast Cancer. Oncol Ther. 2017;5(1):17-29. doi: 10.1007/s40487-017-0046-2. Epub 2017 May 8. Review. PubMed PMID: 28680952; PubMed Central PMCID: PMC5488136.

12: Dogan T, Gnad F, Chan J, Phu L, Young A, Chen MJ, Doll S, Stokes MP, Belvin M, Friedman LS, Kirkpatrick DS, Hoeflich KP, Hatzivassiliou G. Role of the E3 ubiquitin ligase RNF157 as a novel downstream effector linking PI3K and MAPK signaling pathways to the cell cycle. J Biol Chem. 2017 Sep 1;292(35):14311-14324. doi: 10.1074/jbc.M117.792754. Epub 2017 Jun 27. PubMed PMID: 28655764; PubMed Central PMCID: PMC5582827.

13: Zheng X, Goodwin AF, Tian H, Jheon AH, Klein OD. Ras Signaling Regulates Stem Cells and Amelogenesis in the Mouse Incisor. J Dent Res. 2017 Nov;96(12):1438-1444. doi: 10.1177/0022034517717255. Epub 2017 Jun 23. PubMed PMID: 28644741; PubMed Central PMCID: PMC5652855.

14: Rewcastle GW, Kolekar S, Buchanan CM, Gamage SA, Giddens AC, Tsang KY, Kendall JD, Singh R, Lee WJ, Smith GC, Han W, Matthews DJ, Denny WA, Shepherd PR, Jamieson SMF. Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors. Oncotarget. 2017 Jul 18;8(29):47725-47740. doi: 10.18632/oncotarget.17730. PubMed PMID: 28537878; PubMed Central PMCID: PMC5564600.

15: Zhan M, Deng Y, Zhao L, Yan G, Wang F, Tian Y, Zhang L, Jiang H, Chen Y. Design, Synthesis, and Biological Evaluation of Dimorpholine Substituted Thienopyrimidines as Potential Class I PI3K/mTOR Dual Inhibitors. J Med Chem. 2017 May 11;60(9):4023-4035. doi: 10.1021/acs.jmedchem.7b00357. Epub 2017 Apr 24. PubMed PMID: 28409639.

16: Masson GR, Maslen SL, Williams RL. Analysis of phosphoinositide 3-kinase inhibitors by bottom-up electron-transfer dissociation hydrogen/deuterium exchange mass spectrometry. Biochem J. 2017 May 16;474(11):1867-1877. doi: 10.1042/BCJ20170127. PubMed PMID: 28381646; PubMed Central PMCID: PMC5544108.

17: Wang Y, Li J, Chen JJ, Gao X, Huang Z, Shen Q. Multifunctional Nanoparticles Loading with Docetaxel and GDC0941 for Reversing Multidrug Resistance Mediated by PI3K/Akt Signal Pathway. Mol Pharm. 2017 Apr 3;14(4):1120-1132. doi: 10.1021/acs.molpharmaceut.6b01045. Epub 2017 Mar 22. PubMed PMID: 28291364.

18: Shi F, Guo H, Zhang R, Liu H, Wu L, Wu Q, Liu J, Liu T, Zhang Q. The PI3K inhibitor GDC-0941 enhances radiosensitization and reduces chemoresistance to temozolomide in GBM cell lines. Neuroscience. 2017 Mar 27;346:298-308. doi: 10.1016/j.neuroscience.2017.01.032. Epub 2017 Jan 29. PubMed PMID: 28147244.

19: Packer LM, Geng X, Bonazzi VF, Ju RJ, Mahon CE, Cummings MC, Stephenson SA, Pollock PM. PI3K Inhibitors Synergize with FGFR Inhibitors to Enhance Antitumor Responses in FGFR2(mutant) Endometrial Cancers. Mol Cancer Ther. 2017 Apr;16(4):637-648. doi: 10.1158/1535-7163.MCT-16-0415. Epub 2017 Jan 23. PubMed PMID: 28119489.

20: Soler A, Figueiredo AM, Castel P, Martin L, Monelli E, Angulo-Urarte A, Milà-Guasch M, Viñals F, Baselga J, Casanovas O, Graupera M. Therapeutic Benefit of Selective Inhibition of p110α PI3-Kinase in Pancreatic Neuroendocrine Tumors. Clin Cancer Res. 2016 Dec 1;22(23):5805-5817. Epub 2016 May 25. PubMed PMID: 27225693; PubMed Central PMCID: PMC5338478.