SNX-2112 | PF-04928473 | CAS#908112-43-6 | Hsp90 inhibitor

SNX-2112
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 205736

CAS#: 908112-43-6

Description: SNX-2112, also known as PF 04928473, is an Hsp90 inhibitor which is currently undergoing multiple phase 1 clinical trials. In all cell lines, SNX-2112 led to degradation of MET, HER-2, EGFR, and AKT as well as abrogation of Ras/Raf/MEK/MAPK and PI3K/AKT signaling, followed by complete cell cycle arrest.

Chemical Structure

SNX-2112

CAS# 908112-43-6

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205736
Name: SNX-2112
CAS#: 908112-43-6
Chemical Formula: C23H27F3N4O3
Exact Mass: 464.20
Molecular Weight: 464.480
Elemental Analysis: C, 59.47; H, 5.86; F, 12.27; N, 12.06; O, 10.33

Price and Availability

Size	Price	Availability
10mg	USD 110	Ready to ship
25mg	USD 225	Ready to ship
50mg	USD 385	Ready to ship
100mg	USD 685	Ready to ship
200mg	USD 1250	Ready to ship
500mg	USD 2650	Ready to ship
1g	USD 4350	Ready to ship
2g	USD 6450	Ready to ship
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: SNX2112; SNX-2112; SNX 2112; PF 04928473; PF-04928473; PF04928473.

IUPAC/Chemical Name: 4-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)-2-(((1r,4r)-4-hydroxycyclohexyl)amino)benzamide

InChi Key: ZFVRYNYOPQZKDG-MQMHXKEQSA-N

InChi Code: InChI=1S/C23H27F3N4O3/c1-22(2)10-17-19(18(32)11-22)20(23(24,25)26)29-30(17)13-5-8-15(21(27)33)16(9-13)28-12-3-6-14(31)7-4-12/h5,8-9,12,14,28,31H,3-4,6-7,10-11H2,1-2H3,(H2,27,33)/t12-,14-

SMILES Code: O=C(N)C1=CC=C(N2N=C(C(F)(F)F)C3=C2CC(C)(C)CC3=O)C=C1N[C@H]4CC[C@H](O)CC4

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: >5 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#C8R05C15
View CoA: current batch, Lot#A8T05K29

QC Data:

View QC data: current batch, Lot#C8R05C15
View QC data: current batch, Lot#A8T05K29

Safety Data Sheet (SDS):

View Safety Data Sheet (SDS)

Instruction:

View handling instruction

Biological target:	SNX-2112 selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM. SNX-2112 inhibits proliferation in a panel of cancer cell lines (IC50s = 10-50 nM).
In vitro activity:	SNX-2112 has potential in the treatment of non-small cell lung cancer (NSCLC). SNX-2112 promoted cell death and hindered the growth, invasion, and movement of NSCLC cells in vitro. This study identified the mechanism involved, revealing that SNX-2112 suppressed epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway in NSCLC cells. Reference: J Cancer. 2021 Aug 3;12(19):5825-5837. https://pubmed.ncbi.nlm.nih.gov/34475996/
In vivo activity:	SNX-2112 has the potential to improve patient outcome in multiple myeloma (MM) and other blood cancers. In a mouse model, SNX-2112, delivered as SNX-5422, slowed MM growth and extended survival. SNX-2112 also prevented the formation of blood vessels and inhibited bone cell development. Reference: Blood. 2009 Jan 22;113(4):846-55. https://pubmed.ncbi.nlm.nih.gov/18948577/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMSO	47.0	101.19
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.08
	DMF	0.3	0.54
	Ethanol	1.0	2.15

Preparing Stock Solutions

The following data is based on the product molecular weight 464.48 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. Cheng X, Qin L, Deng L, Zhu X, Li Y, Wu X, Zheng Y. SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway. J Cancer. 2021 Aug 3;12(19):5825-5837. doi: 10.7150/jca.56640. PMID: 34475996; PMCID: PMC8408115. 2. Hu L, Wang Y, Chen Z, Fu L, Wang S, Zhang X, Zhang P, Lu X, Jie H, Li M, Wang Y, Liu Z. Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway. Oxid Med Cell Longev. 2019 Mar 25;2019:9675450. doi: 10.1155/2019/9675450. PMID: 31019655; PMCID: PMC6452544. 3. Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55. doi: 10.1182/blood-2008-04-151928. Epub 2008 Oct 23. PMID: 18948577; PMCID: PMC2630270. 4. Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8. doi: 10.1158/1078-0432.CCR-07-1667. PMID: 18172276; PMCID: PMC3203688.
In vitro protocol:	1. Cheng X, Qin L, Deng L, Zhu X, Li Y, Wu X, Zheng Y. SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway. J Cancer. 2021 Aug 3;12(19):5825-5837. doi: 10.7150/jca.56640. PMID: 34475996; PMCID: PMC8408115. 2. Hu L, Wang Y, Chen Z, Fu L, Wang S, Zhang X, Zhang P, Lu X, Jie H, Li M, Wang Y, Liu Z. Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway. Oxid Med Cell Longev. 2019 Mar 25;2019:9675450. doi: 10.1155/2019/9675450. PMID: 31019655; PMCID: PMC6452544.
In vivo protocol:	1. Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55. doi: 10.1182/blood-2008-04-151928. Epub 2008 Oct 23. PMID: 18948577; PMCID: PMC2630270. 2. Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8. doi: 10.1158/1078-0432.CCR-07-1667. PMID: 18172276; PMCID: PMC3203688.

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1: Liu KS, Liu H, Qi JH, Liu QY, Liu Z, Xia M, Xing GW, Wang SX, Wang YF. SNX-2112, an Hsp90 inhibitor, induces apoptosis and autophagy via degradation of Hsp90 client proteins in human melanoma A-375 cells. Cancer Lett. 2011 Dec 17. [Epub ahead of print] PubMed PMID: 22182451.

2: Wang SX, Ju HQ, Liu KS, Zhang JX, Wang X, Xiang YF, Wang R, Liu JY, Liu QY, Xia M, Xing GW, Liu Z, Wang YF. SNX-2112, a novel Hsp90 inhibitor, induces G2/M cell cycle arrest and apoptosis in MCF-7 cells. Biosci Biotechnol Biochem. 2011;75(8):1540-5. Epub 2011 Aug 7. PubMed PMID: 21821931.

3: Chinn DC, Holland WS, Yoon JM, Zwerdling T, Mack PC. Anti-tumor activity of the HSP90 inhibitor SNX-2112 in pediatric cancer cell lines. Pediatr Blood Cancer. 2011 Jul 27. doi: 10.1002/pbc.23270. [Epub ahead of print] PubMed PMID: 21796766.

4: Zhai QQ, Gong GQ, Liu Z, Luo Y, Xia M, Xing GW, You XF, Wang YF. Preclinical pharmacokinetic analysis of SNX-2112, a novel Hsp90 inhibitor, in rats. Biomed Pharmacother. 2011 Mar;65(2):132-6. Epub 2010 Dec 30. PubMed PMID: 21227627.

5: Bachleitner-Hofmann T, Sun MY, Chen CT, Liska D, Zeng Z, Viale A, Olshen AB, Mittlboeck M, Christensen JG, Rosen N, Solit DB, Weiser MR. Antitumor activity of SNX-2112, a synthetic heat shock protein-90 inhibitor, in MET-amplified tumor cells with or without resistance to selective MET Inhibition. Clin Cancer Res. 2011 Jan 1;17(1):122-33. PubMed PMID: 21208906; PubMed Central PMCID: PMC3263825.

6: Zhai QQ, Gong GQ, Luo Y, Wang QD, Xia M, Xing GW, Li YC, Jiang JH, Liu Z, Liu QY, Wang YF. Determination of SNX-2112, a selective Hsp90 inhibitor, in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats. J Pharm Biomed Anal. 2010 Dec 1;53(4):1048-52. Epub 2010 Jul 6. PubMed PMID: 20675090.

7: Jin L, Xiao CL, Lu CH, Xia M, Xing GW, Xiong S, Liu QY, Liu H, Li YC, Ge F, Wang QD, He QY, Wang YF. Transcriptomic and proteomic approach to studying SNX-2112-induced K562 cells apoptosis and anti-leukemia activity in K562-NOD/SCID mice. FEBS Lett. 2009 Jun 18;583(12):1859-66. Epub 2009 May 8. PubMed PMID: 19427857.

8: Rice JW, Veal JM, Barabasz A, Foley B, Fadden P, Scott A, Huang K, Steed P, Hall S. Targeting of multiple signaling pathways by the Hsp90 inhibitor SNX-2112 in EGFR resistance models as a single agent or in combination with erlotinib. Oncol Res. 2009;18(5-6):229-42. PubMed PMID: 20225761.

9: Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55. Epub 2008 Oct 23. PubMed PMID: 18948577; PubMed Central PMCID: PMC2630270.

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SNX-2112 featured