SNX-2112
featured

    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

img
SNX-2112
CAS# 908112-43-6

Theoretical Analysis

MedKoo Cat#: 205736
Name: SNX-2112
CAS#: 908112-43-6
Chemical Formula: C23H27F3N4O3
Exact Mass: 464.20353
Molecular Weight: 464.48
Elemental Analysis: C, 59.47; H, 5.86; F, 12.27; N, 12.06; O, 10.33

Price and Availability

Size Price Availability Quantity
10.0mg USD 90.0 Ready to ship
25.0mg USD 150.0 Ready to ship
50.0mg USD 250.0 Ready to ship
100.0mg USD 450.0 Ready to ship
200.0mg USD 750.0 Ready to ship
500.0mg USD 1650.0 Ready to ship
1.0g USD 2950.0 Ready to ship
2.0g USD 4850.0 Ready to ship
5.0g USD 6950.0 2 Weeks
Click to view more sizes and prices
Bulk inquiry

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

Biological target: SNX-2112 (PF-04928473) selectively binds to the ATP pocket of HSP90α and HSP90β with Ka of 30 nM and 30 nM, uniformly more potent than 17-AAG.
In vitro activity: SNX-2112 exhibited a creditable anti-NSCLC activity in vitro against A549 cells (IC50, 0.50 ± 0.01 μM), H1299 cells (IC50, 1.14 ± 1.11 μM), and H1975 (IC50, 2.36 ± 0.82 μM). As shown in Figure 1, SNX-2112 significantly suppressed cell proliferation of A549, H1299, and H1975 at 24, 48, and 72 h (p < 0.05), especially for A549 at 24 and 72 h (p < 0.001), H1299 at 72 h (p < 0.001), and H1975 at 48 h (p < 0.001). The results suggested the cell viability of A549, H1299, and H1975 was inhibited by SNX-2112, and the inhibition activity increased with treatment time extension. Reference: Front Cell Dev Biol. 2021; 9: 650106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039390/
In vivo activity: SNX-5422 (prodrug of SNX-2112) significantly reduced MM tumor growth in the treatment group (n = 7) compared with control mice (n = 7) (Figure 6A). Comparison of tumor volumes showed statistically significant differences between control versus treatment groups (vs 20 mg/kg, P < .05; vs 40 mg/kg, P < .01; Figure 6A). Kaplan-Meier curves and log-rank analysis showed a mean overall survival of 32 days (95% confidence interval, 24-47 days) in control mice versus 57 days (95% confidence interval, 38-82 days) and 58 days (95% confidence interval, 40-82 days) in the 20 mg/kg and 40 mg/kg SNX-5422-treated groups, respectively (Figure 6B). Reference: Blood. 2009 Jan 22; 113(4): 846–855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630270/

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 0.25 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.

Recalculate based on batch purity %
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. Zhao D, Xu YM, Cao LQ, Yu F, Zhou H, Qin W, Li HJ, He CX, Xing L, Zhou X, Li PQ, Jin X, He Y, He JH, Cao HL. Complex Crystal Structure Determination and in vitro Anti-non-small Cell Lung Cancer Activity of Hsp90 N Inhibitor SNX-2112. Front Cell Dev Biol. 2021 Mar 29;9:650106. doi: 10.3389/fcell.2021.650106. PMID: 33855025; PMCID: PMC8039390. 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. Zhao D, Xu YM, Cao LQ, Yu F, Zhou H, Qin W, Li HJ, He CX, Xing L, Zhou X, Li PQ, Jin X, He Y, He JH, Cao HL. Complex Crystal Structure Determination and in vitro Anti-non-small Cell Lung Cancer Activity of Hsp90 N Inhibitor SNX-2112. Front Cell Dev Biol. 2021 Mar 29;9:650106. doi: 10.3389/fcell.2021.650106. PMID: 33855025; PMCID: PMC8039390. 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.

Molarity Calculator

Calculate the mass, volume, or concentration required for a solution.
=
x
x
g/mol

*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / CoA (available online).

Reconstitution Calculator

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial. Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

=
÷

Dilution Calculator

Calculate the dilution required to prepare a stock solution.
x
=
x

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.



Additional Information