WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 203181
Description: Pilaralisib, also known as XL147, is a Class 1 PI3K kinase family inhibitor with potential antineoplastic activity. XL147 reversibly binds to class 1 PI3Ks in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K signaling pathway; this may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis.
MedKoo Cat#: 203181
Chemical Formula: C25H25ClN6O4S
Exact Mass: 540.13465
Molecular Weight: 541.02
Elemental Analysis: C, 55.50; H, 4.66; Cl, 6.55; N, 15.53; O, 11.83; S, 5.93
Related CAS #: 934526-89-3 956958-53-5.
Synonym: XL147; XL 147; XL-147; SAR245408; SAR-245408; SAR 245408; Pilaralisib.
IUPAC/Chemical Name: 2-amino-N-(3-(N-(3-((2-chloro-5-methoxyphenyl)amino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide.
InChi Key: QINPEPAQOBZPOF-UHFFFAOYSA-N
InChi Code: InChI=1S/C25H25ClN6O4S/c1-25(2,27)24(33)28-15-7-6-8-17(13-15)37(34,35)32-23-22(29-19-9-4-5-10-20(19)30-23)31-21-14-16(36-3)11-12-18(21)26/h4-14H,27H2,1-3H3,(H,28,33)(H,29,31)(H,30,32)
SMILES Code: CC(C)(N)C(NC1=CC=CC(S(=O)(NC2=NC3=CC=CC=C3N=C2NC4=CC(OC)=CC=C4Cl)=O)=C1)=O
Appearance: 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
The following data is based on the product molecular weight 541.02 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.
|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|
1: Shapiro GI, Rodon J, Bedell C, Kwak EL, Baselga J, BraÃ±a I, Pandya SS, Scheffold C, Laird AD, Nguyen LT, Xu Y, Egile C, Edelman G. Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2014 Jan 1;20(1):233-45. doi: 10.1158/1078-0432.CCR-13-1777. Epub 2013 Oct 28. PubMed PMID: 24166903.
2: Rexer BN, Ghosh R, Narasanna A, Estrada MV, Chakrabarty A, Song Y, Engelman JA, Arteaga CL. Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2. Clin Cancer Res. 2013 Oct 1;19(19):5390-401. doi: 10.1158/1078-0432.CCR-13-1038. Epub 2013 Aug 15. PubMed PMID: 23948973; PubMed Central PMCID: PMC3809918.
3: Chakrabarty A, Bhola NE, Sutton C, Ghosh R, Kuba MG, Dave B, Chang JC, Arteaga CL. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors. Cancer Res. 2013 Feb 1;73(3):1190-200. doi: 10.1158/0008-5472.CAN-12-2440. Epub 2012 Nov 29. PubMed PMID: 23204226; PubMed Central PMCID: PMC3563941.
4: Reynolds CP, Kang MH, Carol H, Lock R, Gorlick R, Kolb EA, Kurmasheva RT, Keir ST, Maris JM, Billups CA, Houghton PJ, Smith MA. Initial testing (stage 1) of the phosphatidylinositol 3' kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program. Pediatr Blood Cancer. 2013 May;60(5):791-8. doi: 10.1002/pbc.24301. Epub 2012 Sep 21. PubMed PMID: 23002019.
5: Chakrabarty A, SÃ¡nchez V, Kuba MG, Rinehart C, Arteaga CL. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2718-23. doi: 10.1073/pnas.1018001108. Epub 2011 Feb 28. PubMed PMID: 21368164; PubMed Central PMCID: PMC3286932.
Exelixis is developing XL147 in collaboration with sanofi-aventis. Based on clinical data available to date, XL147 appears to be well tolerated and has shown clinical activity in a range of cancer types. As a result, Exelixis and sanofi-aventis are pursuing a broad clinical development program for XL147, evaluating the compound as a single agent and in multiple combination regimens in a variety of cancer indications. Ongoing clinical trials include a phase 2 trial in endometrial cancer, phase 1b/2 trials in combination with carboplatin and paclitaxel in patients with endometrial, ovarian or non-small cell lung cancer (NSCLC), in combination with erlotinib in patients with NSCLC, and in combination with trastuzumab or trastuzumab and paclitaxel in patients with HER2-positive breast cancer, and a phase 1 trial in patients with solid tumors or lymphoma. (source: http://www.exelixis.com/pipeline/xl147).