ARN-3236 | CAS#1613710-01-2 | SIK2 inhibitor

MedKoo Cat#: 206832 | Name: ARN-3236

Description:

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

ARN-3236 is potent, orally active and selective SIK2 inhibitor. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L. ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy.

Chemical Structure

ARN-3236

CAS#1613710-01-2 (free base)

Theoretical Analysis

MedKoo Cat#: 206832

Name: ARN-3236

CAS#: 1613710-01-2 (free base)

Chemical Formula: C19H16N2O2S

Exact Mass: 336.0932

Molecular Weight: 336.41

Elemental Analysis: C, 67.84; H, 4.79; N, 8.33; O, 9.51; S, 9.53

Price and Availability

Size	Price	Availability
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 1,250.00	Ready to ship
500mg	USD 2,450.00	Ready to ship
1g	USD 3,250.00	Ready to ship
2g	USD 5,650.00	Ready to ship
5g	USD 7,950.00	2 Weeks

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Related CAS #

1613710-01-2 (free base) ARN-3236 HCl

Synonym

ARN-3236; ARN 3236; ARN3236;

IUPAC/Chemical Name

3-(2,4-Dimethoxyphenyl)-4-(3-thienyl)-1H-pyrrolo[2,3-b]pyridine

InChi Key

WEHOIIGXTMKVRG-UHFFFAOYSA-N

InChi Code

InChI=1S/C19H16N2O2S/c1-22-13-3-4-15(17(9-13)23-2)16-10-21-19-18(16)14(5-7-20-19)12-6-8-24-11-12/h3-11H,1-2H3,(H,20,21)

SMILES Code

COC1=CC=C(C2=CNC3=NC=CC(C4=CSC=C4)=C32)C(OC)=C1

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

>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

ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression. ARN-3236 is the first orally available inhibitor of SIK2 to be evaluated against ovarian cancer in preclinical models and shows promise in inhibiting ovarian cancer growth and enhancing paclitaxel chemosensitivity. Salt-inducible kinase 2 (SIK2) is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C8R11B10

QC Data

View QC data: current batch, Lot#C8R11B10

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ARN-3236 is an inhibitor of salt-inducible kinase 2 (SIK2), with IC50s of <1 nM, 21.63 nM and 6.63 nM for SIK2, SIK1 and SIK3, respectively.

In vitro activity:

The SIK2 inhibitor ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures of ovarian cancer cell lines. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L, where the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = -0.642, P = 0.03). ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. In at least three cell lines, a synergistic interaction was observed. ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy. ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression. Reference: Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436602/

In vivo activity:

The antidepressant-like actions of ARN-3236 in mice were explored. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Reference: Front Pharmacol. 2021 Jan 14;11:624429. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840484/

	Solvent	mg/mL	mM
Solubility
	DMSO	65.7	195.21
	Ethanol	2.0	5.95
	DMF	30.0	89.18
	DMSO:PBS (pH 7.2) (1:4)	0.2	0.59

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 336.41 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. Zhou J, Alfraidi A, Zhang S, Santiago-O'Farrill JM, Yerramreddy Reddy VK, Alsaadi A, Ahmed AA, Yang H, Liu J, Mao W, Wang Y, Takemori H, Vankayalapati H, Lu Z, Bast RC Jr. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. doi: 10.1158/1078-0432.CCR-16-1562. Epub 2016 Sep 27. PMID: 27678456; PMCID: PMC5436602. 2. Bon H, Wadhwa K, Schreiner A, Osborne M, Carroll T, Ramos-Montoya A, Ross-Adams H, Visser M, Hoffmann R, Ahmed AA, Neal DE, Mills IG. Salt-inducible kinase 2 regulates mitotic progression and transcription in prostate cancer. Mol Cancer Res. 2015 Apr;13(4):620-635. doi: 10.1158/1541-7786.MCR-13-0182-T. Epub 2014 Dec 29. PMID: 25548099; PMCID: PMC4383640. 3. Liu Y, Tang W, Ji C, Gu J, Chen Y, Huang J, Zhao X, Sun Y, Wang C, Guan W, Liu J, Jiang B. The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway. Front Pharmacol. 2021 Jan 14;11:624429. doi: 10.3389/fphar.2020.624429. PMID: 33519490; PMCID: PMC7840484.

In vitro protocol:

In vivo protocol:

1. Liu Y, Tang W, Ji C, Gu J, Chen Y, Huang J, Zhao X, Sun Y, Wang C, Guan W, Liu J, Jiang B. The Selective SIK2 Inhibitor ARN-3236 Produces Strong Antidepressant-Like Efficacy in Mice via the Hippocampal CRTC1-CREB-BDNF Pathway. Front Pharmacol. 2021 Jan 14;11:624429. doi: 10.3389/fphar.2020.624429. PMID: 33519490; PMCID: PMC7840484.

1: Zhou J, Alfraidi A, Zhang S, Santiago-O'Farrill JM, Yerramreddy Reddy VK, Alsaadi A, Ahmed AA, Yang H, Liu J, Mao W, Wang Y, Takemori H, Vankayalapati H, Lu Z, Bast RC Jr. A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel. Clin Cancer Res. 2017 Apr 15;23(8):1945-1954. doi: 10.1158/1078-0432.CCR-16-1562. Epub 2016 Sep 27. PubMed PMID: 27678456. 2: Bon H, Wadhwa K, Schreiner A, Osborne M, Carroll T, Ramos-Montoya A, Ross-Adams H, Visser M, Hoffmann R, Ahmed AA, Neal DE, Mills IG. Salt-inducible kinase 2 regulates mitotic progression and transcription in prostate cancer. Mol Cancer Res. 2015 Apr;13(4):620-35. doi: 10.1158/1541-7786.MCR-13-0182-T. Epub 2014 Dec 29. PubMed PMID: 25548099; PubMed Central PMCID: PMC4383640. 3: Lombardi MS, Gilliéron C, Dietrich D, Gabay C. SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype. J Leukoc Biol. 2016 May;99(5):711-21. doi: 10.1189/jlb.2A0715-307R. Epub 2015 Nov 20. PubMed PMID: 26590148.