ISA-2011B | CAS#1395347-24-6 | PIP5Kα inhibitor

MedKoo Cat#: 406643 | Name: ISA-2011B

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Description:

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

ISA-2011B is a PIP5Kα (Phosphatidylinositol-4-phosphate 5-kinase-α) inhibitor. The overexpression of PIP5K1α is associated with poor prognosis in prostate cancer and correlates with an elevated level of the androgen receptor. ISA-2011B significantly inhibits growth of tumor cells in xenograft mice, which is mediated by targeting PIP5K1α-associated PI3K/AKT and the downstream survival, proliferation, and invasion pathways. PIP5K1α has high potential as a drug target, and compound ISA-2011B is interesting for further development of targeted cancer therapy.

Chemical Structure

ISA-2011B

CAS#1395347-24-6

Theoretical Analysis

MedKoo Cat#: 406643

Name: ISA-2011B

CAS#: 1395347-24-6

Chemical Formula: C22H18ClN3O4

Exact Mass: 423.0986

Molecular Weight: 423.85

Elemental Analysis: C, 62.34; H, 4.28; Cl, 8.36; N, 9.91; O, 15.10

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 550.00
10mg	USD 950.00

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Synonym

ISA2011B; ISA 2011B; ISA-2011B; ISA2011-B; ISA 2011-B; ISA-2011-B.

IUPAC/Chemical Name

(5S,10aS)-5-(5-chloro-1H-indol-3-yl)-9-methyl-8,9,10a,11-tetrahydro-5H-[1,3]dioxolo[4,5-g]pyrazino[1,2-b]isoquinoline-7,10-dione

InChi Key

FSEZESVJDPKRDS-UWJYYQICSA-N

InChi Code

InChI=1S/C22H18ClN3O4/c1-25-9-20(27)26-17(22(25)28)4-11-5-18-19(30-10-29-18)7-13(11)21(26)15-8-24-16-3-2-12(23)6-14(15)16/h2-3,5-8,17,21,24H,4,9-10H2,1H3/t17-,21-/m0/s1

SMILES Code

O=C(N1[C@H](C2=CNC3=C2C=C(Cl)C=C3)C4=C(C=C5C(OCO5)=C4)C[C@]16[H])CN(C)C6=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, 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

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Product Data

Product Data

Instruction

View handling instruction

Biological target:

ISA-2011B is a PIP5K1α inhibitor with promising anticancer effects .

In vitro activity:

ISA-2011B exhibited a significant inhibitory effect on AR target genes including CDK1 and MMP9 in CRPC cells with wild-type PIP5K1α and in CRPC cells lacking the N-terminal domain of PIP5K1α. Reference: Front Cell Dev Biol. 2022 Mar 21;10:798590. https://pubmed.ncbi.nlm.nih.gov/35386201/

In vivo activity:

This study established 22Rv1 tumors overexpressing AR-V7 in mice, and then treated these mice bearing AR-V7-overexpressing tumors (100-150 mm3 in mean volumes) with ISA-2011B or vehicle control. ISA-2011B-treatment also led to an inhibition in the expression of vimentin, a bio-marker for metastatic tumors, in the infiltrating tumor cells at the invasive front (Figure 3f). Reference: Oncotarget. 2016 Sep 27;7(39):63065-63081. https://pubmed.ncbi.nlm.nih.gov/27588408/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	235.93

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 423.85 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. Wang T, Sarwar M, Whitchurch JB, Collins HM, Green T, Semenas J, Ali A, Roberts CJ, Morris RD, Hubert M, Chen S, El-Schich Z, Wingren AG, Grundström T, Lundmark R, Mongan NP, Gunhaga L, Heery DM, Persson JL. PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer. Front Cell Dev Biol. 2022 Mar 21;10:798590. doi: 10.3389/fcell.2022.798590. PMID: 35386201; PMCID: PMC8979106. 2. Kunkl M, Porciello N, Mastrogiovanni M, Capuano C, Lucantoni F, Moretti C, Persson JL, Galandrini R, Buzzetti R, Tuosto L. ISA-2011B, a Phosphatidylinositol 4-Phosphate 5-Kinase α Inhibitor, Impairs CD28-Dependent Costimulatory and Pro-inflammatory Signals in Human T Lymphocytes. Front Immunol. 2017 Apr 26;8:502. doi: 10.3389/fimmu.2017.00502. PMID: 28491063; PMCID: PMC5405084. 3. Sarwar M, Semenas J, Miftakhova R, Simoulis A, Robinson B, Gjörloff Wingren A, Mongan NP, Heery DM, Johnsson H, Abrahamsson PA, Dizeyi N, Luo J, Persson JL. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells. Oncotarget. 2016 Sep 27;7(39):63065-63081. doi: 10.18632/oncotarget.11757. PMID: 27588408; PMCID: PMC5325347. 4. Semenas J, Hedblom A, Miftakhova RR, Sarwar M, Larsson R, Shcherbina L, Johansson ME, Härkönen P, Sterner O, Persson JL. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3689-98. doi: 10.1073/pnas.1405801111. Epub 2014 Jul 28. PMID: 25071204; PMCID: PMC4156761.

In vitro protocol:

In vivo protocol:

1. Sarwar M, Semenas J, Miftakhova R, Simoulis A, Robinson B, Gjörloff Wingren A, Mongan NP, Heery DM, Johnsson H, Abrahamsson PA, Dizeyi N, Luo J, Persson JL. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells. Oncotarget. 2016 Sep 27;7(39):63065-63081. doi: 10.18632/oncotarget.11757. PMID: 27588408; PMCID: PMC5325347. 2. Semenas J, Hedblom A, Miftakhova RR, Sarwar M, Larsson R, Shcherbina L, Johansson ME, Härkönen P, Sterner O, Persson JL. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3689-98. doi: 10.1073/pnas.1405801111. Epub 2014 Jul 28. PMID: 25071204; PMCID: PMC4156761.

1: Drake JM, Huang J. PIP5K1α inhibition as a therapeutic strategy for prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12578-9. doi: 10.1073/pnas.1413363111. Epub 2014 Aug 12. PubMed PMID: 25118275; PubMed Central PMCID: PMC4156720. 2: Semenas J, Hedblom A, Miftakhova RR, Sarwar M, Larsson R, Shcherbina L, Johansson ME, HÃ¤rkÃ¶nen P, Sterner O, Persson JL. The role of PI3K/AKT-related PIP5K1α and the discovery of its selective inhibitor for treatment of advanced prostate cancer. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3689-98. doi: 10.1073/pnas.1405801111. Epub 2014 Jul 28. PubMed PMID: 25071204; PubMed Central PMCID: PMC4156761.