ASP4132 tosylate | CAS#1640294-30-9 | AMPK activator

MedKoo Cat#: 207128 | Name: ASP4132 tosylate

Description:

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

ASP4132 is an AMPK activator with potential antineoplastic activity. Upon oral administration, ASP4132 affects oxidative phosphorylation in mitochondria of metabolically-active tumor cells, which reduces both energy production and tumor cell proliferation. Mitochondrial oxidative phosphorylation is hyperactivated in tumor cells and plays a key role in the promotion of tumor cell proliferation.

Chemical Structure

ASP4132 tosylate

CAS#1640294-30-9 (tosylate)

Theoretical Analysis

MedKoo Cat#: 207128

Name: ASP4132 tosylate

CAS#: 1640294-30-9 (tosylate)

Chemical Formula: C46H51F3N6O8S2

Exact Mass: 0.0000

Molecular Weight: 937.06

Elemental Analysis: C, 58.96; H, 5.49; F, 6.08; N, 8.97; O, 13.66; S, 6.84

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
200mg	USD 1,950.00	2 Weeks
500mg	USD 3,650.00	2 Weeks

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Related CAS #

1640294-29-6 (free base) 1640294-30-9 (tosylate)

Synonym

ASP4132 tosylate; ASP 4132; ASP-4132; ASP4132

IUPAC/Chemical Name

(6-(1-((6-methoxypyridin-3-yl)methyl)piperidin-4-yl)-1H-benzo[d]imidazol-2-yl)(4-(4-(trifluoromethyl)benzyl)piperazin-1-yl)methanone bis(4-methylbenzenesulfonate)

InChi Key

KDMGCEXVMOJAAC-UHFFFAOYSA-N

InChi Code

InChI=1S/C32H35F3N6O2.2C7H8O3S/c1-43-29-9-4-23(19-36-29)21-39-12-10-24(11-13-39)25-5-8-27-28(18-25)38-30(37-27)31(42)41-16-14-40(15-17-41)20-22-2-6-26(7-3-22)32(33,34)35;2*1-6-2-4-7(5-3-6)11(8,9)10/h2-9,18-19,24H,10-17,20-21H2,1H3,(H,37,38);2*2-5H,1H3,(H,8,9,10)

SMILES Code

O=C(C1=NC2=CC=C(C3CCN(CC4=CC=C(OC)N=C4)CC3)C=C2N1)N5CCN(CC6=CC=C(C(F)(F)F)C=C6)CC5.OS(=O)(C7=CC=C(C)C=C7)=O.OS(=O)(C8=CC=C(C)C=C8)=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

Shelf Life

>3 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:

ASP4132 is an orally active, potent AMPK activator with an EC50 of 18 nM.

In vitro activity:

The resulting in vitro pharmacological properties and aqueous solubility of 28 (ASP4132 tosylate) are summarized in Table 9. Compound 28 showed comparable cell growth inhibitory (IC50 = 0.014 μM) activity against MDA-MB-453 to that of compound 2. Furthermore, 28 showed relatively weak antiproliferative activity against SK-BR-3 (IC50 > 3 μM), indicating that the selectivity of cellular growth inhibitory activity observed in lead compound 2 was maintained in 28. In addition, the aqueous solubility of 28 was significantly higher than that of 2, especially in the Japanese Pharmacopoeia 2nd fluid for disintegration test (JP2: pH = 6.8) with taurocholic acid. Reference: Bioorg Med Chem. 2020 Mar 1;28(5):115307. https://pubmed.ncbi.nlm.nih.gov/32007387/

In vivo activity:

By recording tumor volumes this study found that oral administration of a single dose of ASP4132 (5 mg/kg body weight, for 21 days) largely inhibited NSCLC xenograft growth in SCID mice (Fig. 6A). This concentration was based on the recommendation from the supplier. Volumes of NSCLC xenografts with ASP4132 administration were significantly lower than those of vehicle control xenografts (Fig. 6A). Results showed that ASP4132 oral administration potently suppressed NSCLC xenograft growth in SCID mice (Fig. 6B). At Day-42 all tumors of the two groups were separated through surgery and weighted individually. Results in Fig. 6C demonstrated that ASP4132-treated NSCLC xenografts were dramatically lighter than the control tumors. Importantly, the mice body weights were not significantly different between the ASP4132 group and vehicle control group (Fig. 6D), indicating that mice should be well-tolerated to ASP4132 treatment regimen, and this study did not detect any apparent toxicities. Reference: Cell Death Dis. 2021 Apr; 12(4): 365. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024326/

	Solvent	mg/mL	mM
Solubility
	DMSO	175.0	186.75

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 937.06 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. Xia YC, Zha JH, Sang YH, Yin H, Xu GQ, Zhen J, Zhang Y, Yu BT. AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth. Cell Death Dis. 2021 Apr 6;12(4):365. doi: 10.1038/s41419-021-03655-2. PMID: 33824293; PMCID: PMC8024326. 2. Kuramoto K, Yamada H, Shin T, Sawada Y, Azami H, Yamada T, Nagashima T, Ohnuki K. Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer. Bioorg Med Chem. 2020 Mar 1;28(5):115307. doi: 10.1016/j.bmc.2020.115307. Epub 2020 Jan 8. PMID: 32007387.

In vitro protocol:

In vivo protocol:

1: Xia YC, Zha JH, Sang YH, Yin H, Xu GQ, Zhen J, Zhang Y, Yu BT. AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth. Cell Death Dis. 2021 Apr 6;12(4):365. doi: 10.1038/s41419-021-03655-2. PMID: 33824293; PMCID: PMC8024326. 2: Janku F, LoRusso P, Mansfield AS, Nanda R, Spira A, Wang T, Melhem-Bertrandt A, Sugg J, Ball HA. First-in-human evaluation of the novel mitochondrial complex I inhibitor ASP4132 for treatment of cancer. Invest New Drugs. 2021 Oct;39(5):1348-1356. doi: 10.1007/s10637-021-01112-7. Epub 2021 Apr 8. PMID: 33830407. 3: Kuramoto K, Yamada H, Shin T, Sawada Y, Azami H, Yamada T, Nagashima T, Ohnuki K. Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer. Bioorg Med Chem. 2020 Mar 1;28(5):115307. doi: 10.1016/j.bmc.2020.115307. Epub 2020 Jan 8. PMID: 32007387. 4: Kuramoto K, Sawada Y, Yamada T, Nagashima T, Ohnuki K, Shin T. Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced hERG Inhibitory Activity. Chem Pharm Bull (Tokyo). 2020;68(5):452-465. doi: 10.1248/cpb.c20-00015. PMID: 32378543.