Pilaralisib
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MedKoo CAT#: 203181

CAS#: 934526-89-3

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.


Chemical Structure

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Pilaralisib
CAS# 934526-89-3

Theoretical Analysis

MedKoo Cat#: 203181
Name: Pilaralisib
CAS#: 934526-89-3
Chemical Formula: C25H25ClN6O4S
Exact Mass: 540.13
Molecular Weight: 541.023
Elemental Analysis: C, 55.50; H, 4.66; Cl, 6.55; N, 15.53; O, 11.83; S, 5.93

Price and Availability

Size Price Availability Quantity
50mg USD 250
100mg USD 450
200mg USD 750
500mg USD 1450
1g USD 2650
2g USD 4250
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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

More Info: 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).    

Product Data:
Biological target: Pilaralisib (XL147; SAR245408) is a potent and highly selective class I PI3Ks inhibitor with IC50s of 39 nM, 383 nM, 23 nM and 36 nM for PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ.
In vitro activity: XL147 (SAR245408) is a potent and highly selective inhibitor of class I PI3Ks (α, β, γ, and δ). Moreover, broad kinase selectivity profiling of >130 protein kinases revealed that XL147 is highly selective for class I PI3Ks over other kinases. In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. Reference: Mol Cancer Ther. 2015 Apr;14(4):931-40. https://pubmed.ncbi.nlm.nih.gov/25637314/
In vivo activity: SAR245408 was well tolerated in vivo, and all 44 tested xenograft models were evaluable for efficacy. SAR245408 induced significant differences in EFS distribution compared to control in 29 of 37 (79%) of solid tumor xenografts and in two of seven (29%) ALL xenografts. SAR245408 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity (EFS T/C > 2) in 4 of 37 (11%) solid tumor xenografts. Reference: Pediatr Blood Cancer. 2013 May;60(5):791-8. https://pubmed.ncbi.nlm.nih.gov/23002019/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMF 20.0 36.97
DMSO 60.0 110.90
DMSO:PBS (pH 7.2) (1:30) 0.0 0.06

Preparing Stock Solutions

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.

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. Foster P, Yamaguchi K, Hsu PP, Qian F, Du X, Wu J, Won KA, Yu P, Jaeger CT, Zhang W, Marlowe CK, Keast P, Abulafia W, Chen J, Young J, Plonowski A, Yakes FM, Chu F, Engell K, Bentzien F, Lam ST, Dale S, Yturralde O, Matthews DJ, Lamb P, Laird AD. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models. Mol Cancer Ther. 2015 Apr;14(4):931-40. doi: 10.1158/1535-7163.MCT-14-0833. Epub 2015 Jan 30. PMID: 25637314. 2. 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. PMID: 23002019; PMCID: PMC4684943.
In vitro protocol: 1. Foster P, Yamaguchi K, Hsu PP, Qian F, Du X, Wu J, Won KA, Yu P, Jaeger CT, Zhang W, Marlowe CK, Keast P, Abulafia W, Chen J, Young J, Plonowski A, Yakes FM, Chu F, Engell K, Bentzien F, Lam ST, Dale S, Yturralde O, Matthews DJ, Lamb P, Laird AD. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models. Mol Cancer Ther. 2015 Apr;14(4):931-40. doi: 10.1158/1535-7163.MCT-14-0833. Epub 2015 Jan 30. PMID: 25637314. 2. 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. PMID: 23002019; PMCID: PMC4684943.
In vivo protocol: 1. Foster P, Yamaguchi K, Hsu PP, Qian F, Du X, Wu J, Won KA, Yu P, Jaeger CT, Zhang W, Marlowe CK, Keast P, Abulafia W, Chen J, Young J, Plonowski A, Yakes FM, Chu F, Engell K, Bentzien F, Lam ST, Dale S, Yturralde O, Matthews DJ, Lamb P, Laird AD. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models. Mol Cancer Ther. 2015 Apr;14(4):931-40. doi: 10.1158/1535-7163.MCT-14-0833. Epub 2015 Jan 30. PMID: 25637314. 2. 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. PMID: 23002019; PMCID: PMC4684943.

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1: Shapiro GI, Rodon J, Bedell C, Kwak EL, Baselga J, Braña 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, Sánchez 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.