Bentamapimod | AS-602801 | 848344-36-5 | JNK Inhibitor

MedKoo Cat#: 319883 | Name: Bentamapimod

Description:

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

Bentamapimod, also known as AS602801 and PGL5001, is a JNK Inhibitor. AS602801 induces regression of endometriotic lesions in animal models. AS602801 interrupts immune pathways. Bentamapimod induced regression of endometriotic lesions in endometriosis rodent animal models without suppressing ER action. Endometriosis is an estrogen (ER)-dependent gynecological disease caused by the growth of endometrial tissue at extrauterine sites.

Chemical Structure

Bentamapimod

CAS#848344-36-5

Theoretical Analysis

MedKoo Cat#: 319883

Name: Bentamapimod

CAS#: 848344-36-5

Chemical Formula: C25H23N5O2S

Exact Mass: 457.1572

Molecular Weight: 457.55

Elemental Analysis: C, 65.63; H, 5.07; N, 15.31; O, 6.99; S, 7.01

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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Related CAS #

No Data

Synonym

AS602801; AS-602801; AS 602801; PGL5001; PGL-5001; PGL 5001; Bentamapimod

IUPAC/Chemical Name

2-(1,3-benzothiazol-2-yl)-2-[2-({4-[(morpholin-4-yl)methyl]phenyl}methoxy)pyrimidin-4-yl]acetonitrile

InChi Key

XCPPIJCBCWUBNT-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H23N5O2S/c26-15-20(24-28-22-3-1-2-4-23(22)33-24)21-9-10-27-25(29-21)32-17-19-7-5-18(6-8-19)16-30-11-13-31-14-12-30/h1-10,20H,11-14,16-17H2

SMILES Code

N#CC(C1=NC2=CC=CC=C2S1)C3=NC(OCC4=CC=C(CN5CCOCC5)C=C4)=NC=C3

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, 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

Certificate of Analysis

View CoA: current batch, Lot#C9R09B05

QC Data

View QC data: current batch, Lot#C9R09B05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Bentamapimod (AS 602801) is an ATP-competitive JNK inhibitor with IC50 of 80 nM, 90 nM, and 230 nM for JNK1, JNK2, and JNK3, respectively.

In vitro activity:

AS602801 treatment induced cell death and accordingly decreased the number of viable cells in all three cell lines in a dose-dependent manner, suggesting that AS602801 may have selective cytotoxic activity against neoplastic cells (Figure 1A and 1B). This study next investigated whether cancer stem cells derived from these cell lines (PANC-1 CSLCs, A549 CSLCs, and A2780 CSLCs) were resistant to AS602801-induced cell death. AS602801 induced cell death in these cells as efficiently as in the original cell lines, suggesting that the cancer stem cell and non-cancer stem cell subpopulations within a cell line are equally sensitive to AS602801 (Figure 2A and 2B). GS-Y01 cells, which are patient-derived glioma stem cells, were also tested to examine whether AS602801 has cytotoxic activity against cells established directly from patient tumor tissues. AS602801 also had cytotoxic activity against GS-Y01 cells (Figure 2A and 2B). Reference: Oncotarget. 2016 May 10; 7(19): 27021–27032. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053629/

In vivo activity:

Compared to control or Antide-treated rats, both total c-Jun (Figure 6A-C) and phospho-c-Jun staining (Figure 6D-F) were decreased with bentamapimod treatment. The reduction in phospho-c-Jun was more dramatic (Figure 6E) in mice treated with bentamapimod than the change in total c-Jun (Figure 6B). As expected, signs of apoptosis as measured by TUNEL staining were evident in sections from bentamapimod-treated uteri and Antide-treated uteri, relative to control (Figure 6G-I). Lastly, CD45 staining, reflecting a broad marker for T and B lymphocytes, was suppressed by AS602801, whereas the presence of CD45 was unaffected by Antide treatment (Figure 6L-N). These results suggest that bentamapimod has potential to reduce the number of CD45+ lymphocytes recruited to lesions (perhaps through inhibition of phosphorylated c-Jun) or alternatively to reduce the presence of T or B cells present within lesions, through processes that could include apoptosis. These results confirm an effect of JNK inhibition on the inflammatory and/or immune responses to endometriosis and demonstrate that this effect occurs through a different mechanism than endocrine regulators such as Antide. Reference: Reprod Sci. 2016 Jan; 23(1): 11–23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933194/

	Solvent	mg/mL	mM
Solubility
	DMF	2.0	4.37
	DMSO	13.4	29.35

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 457.55 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. Kuramoto K, Yamamoto M, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C, Okada M. AS602801, an Anti-Cancer Stem Cell Drug Candidate, Suppresses Gap-junction Communication Between Lung Cancer Stem Cells and Astrocytes. Anticancer Res. 2018 Sep;38(9):5093-5099. doi: 10.21873/anticanres.12829. PMID: 30194154. 2. Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32. doi: 10.18632/oncotarget.8395. PMID: 27027242; PMCID: PMC5053629. 3. Chen M, Sun J, Lu C, Chen X, Ba H, Lin Q, Cai J, Dai J. The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model. Oncotarget. 2016 Nov 8;7(45):73903-73911. doi: 10.18632/oncotarget.12094. PMID: 27655677; PMCID: PMC5342022. 4. Palmer SS, Altan M, Denis D, Tos EG, Gotteland JP, Osteen KG, Bruner-Tran KL, Nataraja SG. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23. doi: 10.1177/1933719115600553. Epub 2015 Sep 2. PMID: 26335175; PMCID: PMC5933194.

In vitro protocol:

In vivo protocol:

1. Chen M, Sun J, Lu C, Chen X, Ba H, Lin Q, Cai J, Dai J. The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model. Oncotarget. 2016 Nov 8;7(45):73903-73911. doi: 10.18632/oncotarget.12094. PMID: 27655677; PMCID: PMC5342022. 2. Palmer SS, Altan M, Denis D, Tos EG, Gotteland JP, Osteen KG, Bruner-Tran KL, Nataraja SG. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23. doi: 10.1177/1933719115600553. Epub 2015 Sep 2. PMID: 26335175; PMCID: PMC5933194.

1: Palmer SS, Altan M, Denis D, Tos EG, Gotteland JP, Osteen KG, Bruner-Tran KL, Nataraja SG. Bentamapimod (JNK Inhibitor AS602801) Induces Regression of Endometriotic Lesions in Animal Models. Reprod Sci. 2016 Jan;23(1):11-23. doi: 10.1177/1933719115600553. Epub 2015 Sep 2. PMID: 26335175; PMCID: PMC5933194. 2: Hussein M, Chai DC, Kyama CM, Mwenda JM, Palmer SS, Gotteland JP, D'Hooghe TM. c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study. Fertil Steril. 2016 Mar;105(3):815-824.e5. doi: 10.1016/j.fertnstert.2015.11.022. Epub 2015 Dec 2. PMID: 26654972. 3: Mikuš M, Vitale SG, Ćorić M, Zajec V, Ciebiera M, Carugno J, D'alterio MN, Herman M, Puževski T, Angioni S. State of the art, new treatment strategies, and emerging drugs for non-hormonal treatment of endometriosis: a systematic review of randomized control trials. Gynecol Endocrinol. 2022 Nov;38(11):911-917. doi: 10.1080/09513590.2022.2133105. Epub 2022 Oct 13. PMID: 36237165. 4: Yamamoto M, Suzuki S, Togashi K, Sanomachi T, Seino S, Kitanaka C, Okada M. AS602801 Sensitizes Ovarian Cancer Stem Cells to Paclitaxel by Down-regulating MDR1. Anticancer Res. 2019 Feb;39(2):609-617. doi: 10.21873/anticanres.13154. PMID: 30711936. 5: Chen M, Sun J, Lu C, Chen X, Ba H, Lin Q, Cai J, Dai J. The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model. Oncotarget. 2016 Nov 8;7(45):73903-73911. doi: 10.18632/oncotarget.12094. PMID: 27655677; PMCID: PMC5342022. 6: Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C. The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo. Oncotarget. 2016 May 10;7(19):27021-32. doi: 10.18632/oncotarget.8395. PMID: 27027242; PMCID: PMC5053629. 7: Kuramoto K, Yamamoto M, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C, Okada M. AS602801, an Anti-Cancer Stem Cell Drug Candidate, Suppresses Gap- junction Communication Between Lung Cancer Stem Cells and Astrocytes. Anticancer Res. 2018 Sep;38(9):5093-5099. doi: 10.21873/anticanres.12829. PMID: 30194154. 8: Zhang S, Gong Y, Wang H, Li Z, Huang Y, Fu X, Xiang P, Fan T. AS602801 sensitizes glioma cells to temozolomide and vincristine by blocking gap junction communication between glioma cells and astrocytes. J Cell Mol Med. 2021 Apr;25(8):4062-4072. doi: 10.1111/jcmm.16375. Epub 2021 Feb 20. PMID: 33609076; PMCID: PMC8051707. 9: Yamamoto M, Suzuki S, Togashi K, Sanomachi T, Seino S, Kitanaka C, Okada M. AS602801, an Anticancer Stem Cell Candidate Drug, Reduces Survivin Expression and Sensitizes A2780 Ovarian Cancer Stem Cells to Carboplatin and Paclitaxel. Anticancer Res. 2018 Dec;38(12):6699-6706. doi: 10.21873/anticanres.13038. PMID: 30504379. 10: Dougherty MC, Shibata SB, Clark JJ, Canady FJ, Yates CW, Hansen MR. Reduction of sporadic and neurofibromatosis type 2-associated vestibular schwannoma growth in vitro and in vivo after treatment with the c-Jun N-terminal kinase inhibitor AS602801. J Neurosurg. 2022 Sep 9;138(4):962-971. doi: 10.3171/2022.7.JNS22934. PMID: 36087315; PMCID: PMC10193498.