SAR-405 | CAS#1523406-39-4 | PIK3C3/Vps34 inhibitor

MedKoo Cat#: 406844 | Name: SAR405

Description:

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

SAR-405 is a potent and selective PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Combining SAR405 with everolimus results in a significant synergy on the reduction of cell proliferation using renal tumor cells.

Chemical Structure

SAR405

CAS#1523406-39-4

Theoretical Analysis

MedKoo Cat#: 406844

Name: SAR405

CAS#: 1523406-39-4

Chemical Formula: C19H21ClF3N5O2

Exact Mass: 443.1336

Molecular Weight: 443.86

Elemental Analysis: C, 51.42; H, 4.77; Cl, 7.99; F, 12.84; N, 15.78; O, 7.21

Price and Availability

Size	Price	Availability
25mg	USD 450.00	2 Weeks
50mg	USD 750.00	2 Weeks
100mg	USD 1,250.00	2 Weeks
1g	USD 4,250.00	2 Weeks

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Related CAS #

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Synonym

SAR-405; SAR 405; SAR405.

IUPAC/Chemical Name

(S)-9-((5-chloropyridin-3-yl)methyl)-2-((R)-3-methylmorpholino)-8-(trifluoromethyl)-6,7,8,9-tetrahydro-4H-pyrimido[1,2-a]pyrimidin-4-one

InChi Key

SPDQRCUBFSRAFI-DOMZBBRYSA-N

InChi Code

InChI=1S/C19H21ClF3N5O2/c1-12-11-30-5-4-26(12)16-7-17(29)27-3-2-15(19(21,22)23)28(18(27)25-16)10-13-6-14(20)9-24-8-13/h6-9,12,15H,2-5,10-11H2,1H3/t12-,15+/m1/s1

SMILES Code

O=C1C=C(N2[C@H](C)COCC2)N=C3N(CC4=CC(Cl)=CN=C4)[C@H](C(F)(F)F)CCN31

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 and ethanol

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:

SAR405 inhbits Vps34 inhibitor (IC50=1.2 nM; Kd=1.5 nM). SAR405 inhibits autophagy induced either by starvation or by mTOR inhibition.

In vitro activity:

PIK3C3 inhibitors, like SAR405, have potential therapeutic application in cancer. SAR405 inhibited the catalytic activity of PIK3C3, disrupting vesicle trafficking from late endosomes to lysosomes. SAR405 treatment also inhibited autophagy induced either by starvation or by MTOR inhibition. A combination of SAR405 with everolimus resulted in a significant synergy on the reduction of cell proliferation using renal tumor cells. Reference: Autophagy. 2015 Apr 3;11(4):725-6. https://pubmed.ncbi.nlm.nih.gov/25905679/

In vivo activity:

In this study, SAR405 attenuated the cytotoxicity induced by doxorubicin (DOX) and provides protection against anthracycline-induced cardiotoxicity (AIC) in a chronic AIC mouse model. A combination of dexrazoxane and SAR405 was effective in protecting cells against DOX-induced cardiotoxicity in vivo. By inhibiting autophagy at its early phase, SAR405 offered a promising therapeutic approach for preventing AIC when combined with dexrazoxane. Reference: Cell Biol Toxicol. 2023 Sep 28. https://pubmed.ncbi.nlm.nih.gov/37768392/

	Solvent	mg/mL	mM
Solubility
	DMSO	89.0	200.52
	Ethanol	89.0	200.52

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 443.86 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. Stempels FC, Janssens MH, Ter Beest M, Mesman RJ, Revelo NH, Ioannidis M, van den Bogaart G. Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis. FEBS Lett. 2022 Feb;596(4):491-509. doi: 10.1002/1873-3468.14280. Epub 2022 Jan 21. PMID: 35007347. 2. Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015 Apr 3;11(4):725-6. doi: 10.1080/15548627.2015.1033601. PMID: 25905679; PMCID: PMC4502822. 3. Sun X, Du J, Meng H, Liu F, Yang N, Deng S, Wan H, Ye D, Song E, Zeng H. Targeting autophagy with SAR405 alleviates doxorubicin-induced cardiotoxicity. Cell Biol Toxicol. 2023 Sep 28. doi: 10.1007/s10565-023-09831-8. Epub ahead of print. PMID: 37768392. 4. Li K, Chen HS, Li D, Li HH, Wang J, Jia L, Wu PF, Long LH, Hu ZL, Chen JG, Wang F. SAR405, a Highly Specific VPS34 Inhibitor, Disrupts Auditory Fear Memory Consolidation of Mice via Facilitation of Inhibitory Neurotransmission in Basolateral Amygdala. Biol Psychiatry. 2019 Feb 1;85(3):214-225. doi: 10.1016/j.biopsych.2018.07.026. Epub 2018 Aug 16. Erratum in: Biol Psychiatry. 2019 Nov 15;86(10):801. PMID: 30253884.

In vitro protocol:

In vivo protocol:

1. Sun X, Du J, Meng H, Liu F, Yang N, Deng S, Wan H, Ye D, Song E, Zeng H. Targeting autophagy with SAR405 alleviates doxorubicin-induced cardiotoxicity. Cell Biol Toxicol. 2023 Sep 28. doi: 10.1007/s10565-023-09831-8. Epub ahead of print. PMID: 37768392. 2. Li K, Chen HS, Li D, Li HH, Wang J, Jia L, Wu PF, Long LH, Hu ZL, Chen JG, Wang F. SAR405, a Highly Specific VPS34 Inhibitor, Disrupts Auditory Fear Memory Consolidation of Mice via Facilitation of Inhibitory Neurotransmission in Basolateral Amygdala. Biol Psychiatry. 2019 Feb 1;85(3):214-225. doi: 10.1016/j.biopsych.2018.07.026. Epub 2018 Aug 16. Erratum in: Biol Psychiatry. 2019 Nov 15;86(10):801. PMID: 30253884.

1: Pasquier B. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells. Autophagy. 2015 Apr 3;11(4):725-6. doi: 10.1080/15548627.2015.1033601. PubMed PMID: 25905679; PubMed Central PMCID: PMC4502822. 2: Marsh T, Debnath J. Ironing out VPS34 inhibition. Nat Cell Biol. 2015 Jan;17(1):1-3. PubMed PMID: 25679028. 3: Ronan B, Flamand O, Vescovi L, Dureuil C, Durand L, Fassy F, Bachelot MF, Lamberton A, Mathieu M, Bertrand T, Marquette JP, El-Ahmad Y, Filoche-Romme B, Schio L, Garcia-Echeverria C, Goulaouic H, Pasquier B. A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy. Nat Chem Biol. 2014 Dec;10(12):1013-9. doi: 10.1038/nchembio.1681. Epub 2014 Oct 19. PubMed PMID: 25326666.