WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 202226
CAS#: 1013101-36-4
Description: PF-04691502 is a PI3K/mTOR kinase inhibitor , is also an agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PF-04691502 inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR.
MedKoo Cat#: 202226
Name: PF-04691502
CAS#: 1013101-36-4
Chemical Formula: C22H27N5O4
Exact Mass: 425.2063
Molecular Weight: 425.48
Elemental Analysis: C, 62.10; H, 6.40; N, 16.46; O, 15.04
Synonym: PF04691502; PF 04691502; PF-04691502; PF4691502; PF 4691502; PF-4691502.
IUPAC/Chemical Name: 2-amino-8-((1r,4r)-4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one
InChi Key: XDLYKKIQACFMJG-WKILWMFISA-N
InChi Code: InChI=1S/C22H27N5O4/c1-13-17-11-18(14-3-8-19(30-2)24-12-14)21(29)27(20(17)26-22(23)25-13)15-4-6-16(7-5-15)31-10-9-28/h3,8,11-12,15-16,28H,4-7,9-10H2,1-2H3,(H2,23,25,26)/t15-,16-
SMILES Code: O=C1C(C2=CC=C(OC)N=C2)=CC3=C(C)N=C(N)N=C3N1[C@H]4CC[C@H](OCCO)CC4
Appearance: Solid powder
Purity: >97 % (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
Shelf Life: >5 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: | PF-04691502 is an inhibitor of PI3K and mTOR. PF-04691502 binds to human PI3Kα, β, δ, γ and mTOR with Kis of 1.8, 2.1, 1.6, 1.9 and 16 nM, respectively. |
| In vitro activity: | This study treated QGP-1 and BON cells with PF-04691502 (500 nM) to test the duration of PI3K pathway inhibition (Figure 2C). The expression of pAkt was inhibited in both QGP-1 and BON cells at 24, 48 and 72 h. Similarly, expression of pS6 (Ser235/236), which is a key regulator of 40 S ribosome subunit biogenesis, was inhibited in both cell lines. Finally, this study assessed the expression of p4EBP-1 (Thr37/46), which plays a critical role in translational mRNA complex assembly and found that PF-04691502 (500 nM) inhibited expression of this protein at all time points; p4EBP-1 expression was markedly attenuated at 24 and 48 h and completely inhibited at 72 h. A single treatment with PF-04691502 not only demonstrated sustained inhibition for the 24 h period in QGP-1 and BON cells (Figure 2B), but also attenuated pAkt, pS6 and p4EBP-1 at 24 h in NT-3 cells (data not shown). Moreover, these results demonstrate that PF-04691502 can effectively inhibit PI3K/mTOR pathway components in both QGP-1 and BON cells for at least 72 h. Reference: Cells. 2021 May 20;10(5):1261. https://pubmed.ncbi.nlm.nih.gov/34065268/ |
| In vivo activity: | Finally, this study tested the antitumor activity of PF-502 (PF-04691502) in vivo using a xenograft mouse model. HH cells were transplanted subcutaneously into the flank of nude mice. When the tumors reached a 300 mm3 mean volume, the mice were randomized into two groups (eight mice per group): the group treated with PF-502 and the vehicle control group. Immunohistochemistry analysis of tumor specimens harvested 1 hour after PF-502 injection, confirmed the inhibition of TORC1 and TORC2 signaling compared with the control group, as measured by P-S6RP(Ser235/236) and P-AKT(Ser473) (Supplementary Figure S5). PF-502 exhibited robust antitumor activity from day 4 of treatment (Figure 5a), reaching significance on day 13 (P < 0.005). At the end of the treatment, the tumor size in the PF-502-treated group was 43% of the control group (400 ± 57 mm3 vs 936 ± 158 mm3, P < 0.001). Accordingly, the mean tumor weight in the PF-502 group was 36% of the controls (0.2 ± 0.05 g vs 0.56 ± 0.05 g, P < 0.001) (Figure 5b). Furthermore, the Kaplan-Meier curve revealed PF-502 treatment prolongs survival: The control group showed a median time-to-event of 19 days while all, but one, PF-502-treated mice, did not reach the predefined endpoint by the end of the experiment (day 28, P < 0.005, Figure 5c). Reference: J Invest Dermatol. 2020 May;140(5):1045-1053.e6. https://pubmed.ncbi.nlm.nih.gov/31682844/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 14.0 | 32.9 |
The following data is based on the product molecular weight 425.48 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 |
| Formulation protocol: | 1. Chow Z, Johnson J, Chauhan A, Izumi T, Cavnar M, Weiss H, Townsend CM Jr, Anthony L, Wasilchenko C, Melton ML, Schrader J, Evers BM, Rychahou P. PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors. Cells. 2021 May 20;10(5):1261. doi: 10.3390/cells10051261. PMID: 34065268. 2. Yuan J, Mehta PP, Yin MJ, Sun S, Zou A, Chen J, Rafidi K, Feng Z, Nickel J, Engebretsen J, Hallin J, Blasina A, Zhang E, Nguyen L, Sun M, Vogt PK, McHarg A, Cheng H, Christensen JG, Kan JL, Bagrodia S. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity. Mol Cancer Ther. 2011 Nov;10(11):2189-99. doi: 10.1158/1535-7163.MCT-11-0185. Epub 2011 Jul 12. PMID: 21750219. 3. Bresin A, Cristofoletti C, Caprini E, Cantonetti M, Monopoli A, Russo G, Narducci MG. Preclinical Evidence for Targeting PI3K/mTOR Signaling with Dual-Inhibitors as a Therapeutic Strategy against Cutaneous T-Cell Lymphoma. J Invest Dermatol. 2020 May;140(5):1045-1053.e6. doi: 10.1016/j.jid.2019.08.454. Epub 2019 Nov 1. PMID: 31682844. 4. Blunt MD, Carter MJ, Larrayoz M, Smith LD, Aguilar-Hernandez M, Cox KL, Tipton T, Reynolds M, Murphy S, Lemm E, Dias S, Duncombe A, Strefford JC, Johnson PW, Forconi F, Stevenson FK, Packham G, Cragg MS, Steele AJ. The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits microenvironmental signaling in CLL and the Eµ-TCL1 mouse model. Blood. 2015 Jun 25;125(26):4032-41. doi: 10.1182/blood-2014-11-610329. Epub 2015 May 8. PMID: 25957390. |
| In vitro protocol: | 1. Chow Z, Johnson J, Chauhan A, Izumi T, Cavnar M, Weiss H, Townsend CM Jr, Anthony L, Wasilchenko C, Melton ML, Schrader J, Evers BM, Rychahou P. PI3K/mTOR Dual Inhibitor PF-04691502 Is a Schedule-Dependent Radiosensitizer for Gastroenteropancreatic Neuroendocrine Tumors. Cells. 2021 May 20;10(5):1261. doi: 10.3390/cells10051261. PMID: 34065268. 2. Yuan J, Mehta PP, Yin MJ, Sun S, Zou A, Chen J, Rafidi K, Feng Z, Nickel J, Engebretsen J, Hallin J, Blasina A, Zhang E, Nguyen L, Sun M, Vogt PK, McHarg A, Cheng H, Christensen JG, Kan JL, Bagrodia S. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity. Mol Cancer Ther. 2011 Nov;10(11):2189-99. doi: 10.1158/1535-7163.MCT-11-0185. Epub 2011 Jul 12. PMID: 21750219. |
| In vivo protocol: | 1. Bresin A, Cristofoletti C, Caprini E, Cantonetti M, Monopoli A, Russo G, Narducci MG. Preclinical Evidence for Targeting PI3K/mTOR Signaling with Dual-Inhibitors as a Therapeutic Strategy against Cutaneous T-Cell Lymphoma. J Invest Dermatol. 2020 May;140(5):1045-1053.e6. doi: 10.1016/j.jid.2019.08.454. Epub 2019 Nov 1. PMID: 31682844. 2. Blunt MD, Carter MJ, Larrayoz M, Smith LD, Aguilar-Hernandez M, Cox KL, Tipton T, Reynolds M, Murphy S, Lemm E, Dias S, Duncombe A, Strefford JC, Johnson PW, Forconi F, Stevenson FK, Packham G, Cragg MS, Steele AJ. The PI3K/mTOR inhibitor PF-04691502 induces apoptosis and inhibits microenvironmental signaling in CLL and the Eµ-TCL1 mouse model. Blood. 2015 Jun 25;125(26):4032-41. doi: 10.1182/blood-2014-11-610329. Epub 2015 May 8. PMID: 25957390. |
1. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity [Erratum to document cited in CA155:552621] By Liu, Kevin K.-C.; Zhu, Jin Jiang; Smith, Graham L.; Yin, Min-Jean; Bailey, Simon; Chen, Jeffrey H.; Hu, Qiyue; Huang, Qinhua; Li, Chunze; Li, Qing J.; et al From ACS Medicinal Chemistry Letters, Ahead of Print.
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3. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity By Liu, Kevin K.-C.; Zhu, Jin Jiang; Smith, Graham L.; Yin, Min-Jean; Bailey, Simon; Chen, Jeffrey H.; Hu, Qiyue; Huang, Qinhua; Li, Chunze; Li, Qing J.; et al From ACS Medicinal Chemistry Letters (2011), 2(11), 809-813.
4. In vivo activity of combined PI3K/mTOR and MEK inhibition in a KrasG12D;Pten deletion mouse model of ovarian cancer By Kinross, Kathryn M.; Brown, Daniel V.; Kleinschmidt, Margarete; Jackson, Susan; Christensen, James; Cullinane, Carleen; Hicks, Rodney J.; Johnstone, Ricky W.; McArthur, Grant A. From Molecular Cancer Therapeutics (2011), 10(8), 1440-1449.
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7. mTOR pathway inhibitors for treating ocular disorders By Nivaggioli, Thierry; Weber, David A.; Dor, Philippe Jm; Reilly, Philip From PCT Int. Appl. (2010), WO 2010129622 A1 20101111.
8. Pyrido[2, 3-d]pyrimidinone compounds as PI3 inhibitors and their preparation, pharmaceutical compositions and use in the treatment of abnormal cell growth By Cheng, Hengmiao; Bhumralkar, Dilip; Dress, Klaus Ruprecht; Hoffman, Jacqui Elizabet; Johnson, Mary Catherine; Kania, Robert Steven; Le, Phuong Thi Quy; Nambu, Michell David; Pairish, Mason Alan; Plewe, Michael Bruno; et al From PCT Int. Appl. (2008), WO 2008032162 A1 20080320.
