Samotolisib | LY3023414 | 1386874-06-1 | PI3K/mTOR inhibitor

MedKoo Cat#: 206214 | Name: Samotolisib

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Description:

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

Samotolisib, also known as LY3023414, is a small molecule that has been shown in vitro to be a selective ATP-competitive inhibitor of PI3Kα and mTOR, DNA-PK, and other class I PI3K family members. In vitro, LY3023414 has demonstrated inhibitory activity against PI3K and mTOR in tumor cells, as well as antiproliferative activity and cell cycle effects. In addition, in vitro, LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway. LY3023414 is being investigated in a phase I clinical trial.

Chemical Structure

Samotolisib

CAS#1386874-06-1

Theoretical Analysis

MedKoo Cat#: 206214

Name: Samotolisib

CAS#: 1386874-06-1

Chemical Formula: C23H26N4O3

Exact Mass: 406.2005

Molecular Weight: 406.49

Elemental Analysis: C, 67.96; H, 6.45; N, 13.78; O, 11.81

Price and Availability

Size	Price	Availability
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
500mg	USD 3,950.00	2 Weeks
1g	USD 4,650.00	2 Weeks

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Related CAS #

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Synonym

LY3023414; LY-3023414; LY 3023414; Samotolisib

IUPAC/Chemical Name

(S)-8-(5-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxypropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

InChi Key

ACCFLVVUVBJNGT-AWEZNQCLSA-N

InChi Code

InChI=1S/C23H26N4O3/c1-14(30-5)13-27-21-18-9-15(16-8-17(11-24-10-16)23(2,3)29)6-7-19(18)25-12-20(21)26(4)22(27)28/h6-12,14,29H,13H2,1-5H3/t14-/m0/s1

SMILES Code

O=C(N1C[C@@H](OC)C)N(C)C2=C1C3=CC(C4=CC(C(C)(O)C)=CN=C4)=CC=C3N=C2

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

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Samotolisib potently and selectively inhibits class I PI3K isoforms, DNA-PK, and mTORC1/2 with IC50s of 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. Samotolisib potently inhibits mTORC1/2 at low nanomolar concentrations.

In vitro activity:

Samotolisib demonstrated cytotoxicity and induced cell cycle arrest and apoptosis in both established and patient-derived human skin squamous cell carcinoma (SCC) cells. Samotolisib had no cytotoxic or pro-apoptotic effects on normal human skin cells. Mechanistically, Samotolisib blocked the PI3K-AKT-mTOR pathway in skin SCC cells by dephosphorylating key substrates, including P85, AKT, and S6K1. Reference: Biochem Biophys Res Commun. 2017 Aug 19;490(2):385-392. https://pubmed.ncbi.nlm.nih.gov/28623128/

In vivo activity:

In an anal cancer murine model, topical samotolisib treatment decreased microscopic evidence of squamous cell carcinoma when starting treatment at 15 wk of age in male mice. Reference: J Surg Res. 2023 Feb;282:137-146. https://pubmed.ncbi.nlm.nih.gov/36274448/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	123.01

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 406.49 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. Sakamoto Y, Yamagishi S, Tanizawa Y, Tajimi M, Okusaka T, Ojima H. PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established patient-derived cell panel assay. Jpn J Clin Oncol. 2018 Apr 1;48(4):396-399. doi: 10.1093/jjco/hyy011. PMID: 29474549. 2. Zou Y, Ge M, Wang X. Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo. Biochem Biophys Res Commun. 2017 Aug 19;490(2):385-392. doi: 10.1016/j.bbrc.2017.06.052. Epub 2017 Jun 13. PMID: 28623128. 3. Gunder LC, Moyer TH, Johnson HR, Auyeung AS, Leverson GE, Zhang W, Matkowskyj KA, Carchman EH. Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. J Surg Res. 2023 Feb;282:137-146. doi: 10.1016/j.jss.2022.09.025. Epub 2022 Oct 20. PMID: 36274448. 4. Zhao YY, Wu DM, He M, Zhang F, Zhang T, Liu T, Li J, Li L, Xu Y. Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4. Front Pharmacol. 2021 Aug 13;12:726198. doi: 10.3389/fphar.2021.726198. PMID: 34483936; PMCID: PMC8414251.

In vitro protocol:

In vivo protocol:

1. Gunder LC, Moyer TH, Johnson HR, Auyeung AS, Leverson GE, Zhang W, Matkowskyj KA, Carchman EH. Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. J Surg Res. 2023 Feb;282:137-146. doi: 10.1016/j.jss.2022.09.025. Epub 2022 Oct 20. PMID: 36274448. 2. Zhao YY, Wu DM, He M, Zhang F, Zhang T, Liu T, Li J, Li L, Xu Y. Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4. Front Pharmacol. 2021 Aug 13;12:726198. doi: 10.3389/fphar.2021.726198. PMID: 34483936; PMCID: PMC8414251.

1: Laetsch TW, Ludwig K, Williams PM, Roy-Chowdhuri S, Patton DR, Coffey B, Reid JM, Piao J, Saguilig L, Alonzo TA, Berg SL, Mhlanga J, Fox E, Weigel BJ, Hawkins DS, Mooney MM, Takebe N, Tricoli JV, Janeway KA, Seibel NL, Parsons DW. Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D. JCO Precis Oncol. 2024 Sep;8:e2400258. doi: 10.1200/PO.24.00258. PMID: 39298693. 2: Yan K, Balijepalli C, Gullapalli L, Joshy J, Kotum S, Druyts E. Efficacy and safety of interventions for metastatic castration resistant prostate cancer (mCRPC) patients progressing on androgen receptor-axis-targeted (ARAT) therapy: a systematic literature review. Curr Med Res Opin. 2024 Aug 27:1-12. doi: 10.1080/03007995.2024.2395435. Epub ahead of print. PMID: 39166959. 3: Sen A, Khan S, Rossetti S, Broege A, MacNeil I, DeLaForest A, Molden J, Davis L, Iversrud C, Seibel M, Kopher R, Schulz S, Laing L. Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway. Mol Oncol. 2024 Aug 2. doi: 10.1002/1878-0261.13703. Epub ahead of print. PMID: 39092562. 4: Gunder LC, Moyer TH, Johnson HR, Auyeung AS, Leverson GE, Zhang W, Matkowskyj KA, Carchman EH. Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. J Surg Res. 2023 Feb;282:137-146. doi: 10.1016/j.jss.2022.09.025. Epub 2022 Oct 20. PMID: 36274448. 5: Choudhury AD. PTEN-PI3K pathway alterations in advanced prostate cancer and clinical implications. Prostate. 2022 Aug;82 Suppl 1:S60-S72. doi: 10.1002/pros.24372. PMID: 35657152. 6: Sweeney CJ, Percent IJ, Babu S, Cultrera JL, Mehlhaff BA, Goodman OB, Morris DS, Schnadig ID, Albany C, Shore ND, Sieber PR, Guba SC, Zhang W, Wacheck V, Donoho GP, Szpurka AM, Callies S, Lin BK, Bendell JC. Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2022 Jun 1;28(11):2237-2247. doi: 10.1158/1078-0432.CCR-21-2326. PMID: 35363301; PMCID: PMC9662871. 7: Zhao YY, Wu DM, He M, Zhang F, Zhang T, Liu T, Li J, Li L, Xu Y. Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4. Front Pharmacol. 2021 Aug 13;12:726198. doi: 10.3389/fphar.2021.726198. PMID: 34483936; PMCID: PMC8414251. 8: Hong DS, Moore KN, Bendell JC, Karp DD, Wang JS, Ulahannan SV, Jones S, Wu W, Donoho GP, Ding Y, Capen A, Wang X, Bence Lin A, Patel MR. Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor. Clin Cancer Res. 2021 Apr 1;27(7):1864-1874. doi: 10.1158/1078-0432.CCR-20-3242. Epub 2021 Jan 25. PMID: 33495309. 9: Wu CP, Hung CY, Lusvarghi S, Huang YH, Tseng PJ, Hung TH, Yu JS, Ambudkar SV. Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines. Biochem Pharmacol. 2020 Oct;180:114137. doi: 10.1016/j.bcp.2020.114137. Epub 2020 Jul 4. PMID: 32634436; PMCID: PMC7606332.