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MedKoo Cat#: 202045 | Name: TAE684
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Description:

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

TAE684, also known as NVP-TAE684, is a highly potent and selective small-molecule ALK inhibitor, which blocked the growth of ALCL-derived and ALK-dependent cell lines with IC(50) values between 2 and 10 nM . TAE684 is also a potent inhibitor of LRRK2 kinase activity (IC(50) of 7.8nM against wild-type LRRK2, 6.1nM against the G2019S mutant).

Chemical Structure

TAE684
TAE684
CAS#761439-42-3

Theoretical Analysis

MedKoo Cat#: 202045

Name: TAE684

CAS#: 761439-42-3

Chemical Formula: C30H40ClN7O3S

Exact Mass: 613.2602

Molecular Weight: 614.20

Elemental Analysis: C, 58.66; H, 6.56; Cl, 5.77; N, 15.96; O, 7.81; S, 5.22

Price and Availability

Size Price Availability Quantity
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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Synonym
TAE 684, TAE684, TAE-684, NVP-TAE 684, NVP-TAE684, NVP-TAE-684
IUPAC/Chemical Name
5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidine-2,4-diamine
InChi Key
QQWUGDVOUVUTOY-UHFFFAOYSA-N
InChi Code
InChI=1S/C30H40ClN7O3S/c1-21(2)42(39,40)28-8-6-5-7-26(28)33-29-24(31)20-32-30(35-29)34-25-10-9-23(19-27(25)41-4)37-13-11-22(12-14-37)38-17-15-36(3)16-18-38/h5-10,19-22H,11-18H2,1-4H3,(H2,32,33,34,35)
SMILES Code
CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5S(=O)(C(C)C)=O)=N4)C(OC)=C3)CC2)CC1
Appearance
Pale yellow 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
More Info
Biological target:
NVP-TAE 684 (TAE 684) is an ALK inhibitor which blocks the growth of ALCL-derived and ALK-dependent cell lines with IC50 values between 2 and 10 nM.
In vitro activity:
As shown in Fig. 4 C and D, TAE684 induced G1 phase arrest in a time-dependent manner. After 72 h of treatment with TAE684 (25 nM), 72% of Karpas-299 cells were arrested in G1 phase compared with 26% of cells in G1 phase in DMSO-treated controls. The number of cells in S phase was reduced from 60% to 14% (Fig. 4 C and D). Collectively, these data suggest that TAE684 inhibits the growth of ALCL (anaplastic large-cell lymphomas) cells by both inhibiting the progression of cell cycle and induction of apoptosis. Reference: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765448/
In vivo activity:
TAE684 was administered at 1, 3, and 10 mg/kg once daily by oral gavage to mice starting 72 h after Karpas-299 i.v. injection. After 2 weeks of treatment, a 100-fold reduction in bioluminescence signal was observed in the 3- and 10-mg/kg treatment groups. Although the compound was not efficacious at 1 mg/kg, after 4 weeks of treatment with TAE684 at 3 and 10 mg/kg, there was a significant (P = 0.005) delay in lymphoma development and 100- to 1,000-fold reduction in luminescence signal (Fig. 5 B–D). Reference: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765448/
Solvent mg/mL mM
Solubility
DMSO 6.9 11.23
DMF 20.0 32.56
DMF:PBS (pH 7.2) (1:1) 0.5 0.81
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 614.20 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. Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. doi: 10.1073/pnas.0609412103. Epub 2006 Dec 21. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. PMID: 17185414; PMCID: PMC1765448.
In vitro protocol:
1. Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. doi: 10.1073/pnas.0609412103. Epub 2006 Dec 21. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. PMID: 17185414; PMCID: PMC1765448.
In vivo protocol:
1. Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. doi: 10.1073/pnas.0609412103. Epub 2006 Dec 21. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. PMID: 17185414; PMCID: PMC1765448.
1: Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):270-5. doi: 10.1073/pnas.0609412103. Epub 2006 Dec 21. Erratum in: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2025. PMID: 17185414; PMCID: PMC1765448. 2: McDermott U, Iafrate AJ, Gray NS, Shioda T, Classon M, Maheswaran S, Zhou W, Choi HG, Smith SL, Dowell L, Ulkus LE, Kuhlmann G, Greninger P, Christensen JG, Haber DA, Settleman J. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res. 2008 May 1;68(9):3389-95. doi: 10.1158/0008-5472.CAN-07-6186. PMID: 18451166. 3: Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, Choi HG, Kim J, Chiang D, Thomas R, Lee J, Richards WG, Sugarbaker DJ, Ducko C, Lindeman N, Marcoux JP, Engelman JA, Gray NS, Lee C, Meyerson M, Jänne PA. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008 Jul 1;14(13):4275-83. doi: 10.1158/1078-0432.CCR-08-0168. PMID: 18594010; PMCID: PMC3025451. 4: George RE, Sanda T, Hanna M, Fröhling S, Luther W 2nd, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008 Oct 16;455(7215):975-8. doi: 10.1038/nature07397. PMID: 18923525; PMCID: PMC2587486. 5: Schönherr C, Yang HL, Vigny M, Palmer RH, Hallberg B. Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells. Oncogene. 2010 May 13;29(19):2817-30. doi: 10.1038/onc.2010.27. Epub 2010 Mar 1. PMID: 20190816. 6: Van Roosbroeck K, Cools J, Dierickx D, Thomas J, Vandenberghe P, Stul M, Delabie J, De Wolf-Peeters C, Marynen P, Wlodarska I. ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions. Haematologica. 2010 Mar;95(3):509-13. doi: 10.3324/haematol.2009.014761. PMID: 20207848; PMCID: PMC2833084. 7: Ma H, Togawa A, Soda K, Zhang J, Lee S, Ma M, Yu Z, Ardito T, Czyzyk J, Diggs L, Joly D, Hatakeyama S, Kawahara E, Holzman L, Guan JL, Ishibe S. Inhibition of podocyte FAK protects against proteinuria and foot process effacement. J Am Soc Nephrol. 2010 Jul;21(7):1145-56. doi: 10.1681/ASN.2009090991. Epub 2010 Jun 3. PMID: 20522532; PMCID: PMC3152231. 8: Bossi RT, Saccardo MB, Ardini E, Menichincheri M, Rusconi L, Magnaghi P, Orsini P, Avanzi N, Borgia AL, Nesi M, Bandiera T, Fogliatto G, Bertrand JA. Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors. Biochemistry. 2010 Aug 17;49(32):6813-25. doi: 10.1021/bi1005514. PMID: 20695522. 9: Chun MG, Mao JH, Chiu CW, Balmain A, Hanahan D. Polymorphic genetic control of tumor invasion in a mouse model of pancreatic neuroendocrine carcinogenesis. Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17268-73. doi: 10.1073/pnas.1012705107. Epub 2010 Sep 20. PMID: 20855625; PMCID: PMC2951397. 10: Ardini E, Magnaghi P, Orsini P, Galvani A, Menichincheri M. Anaplastic Lymphoma Kinase: role in specific tumours, and development of small molecule inhibitors for cancer therapy. Cancer Lett. 2010 Dec 28;299(2):81-94. doi: 10.1016/j.canlet.2010.09.001. Epub 2010 Oct 8. PMID: 20934803. 11: Chen Z, Sasaki T, Tan X, Carretero J, Shimamura T, Li D, Xu C, Wang Y, Adelmant GO, Capelletti M, Lee HJ, Rodig SJ, Borgman C, Park SI, Kim HR, Padera R, Marto JA, Gray NS, Kung AL, Shapiro GI, Jänne PA, Wong KK. Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010 Dec 1;70(23):9827-36. doi: 10.1158/0008-5472.CAN-10-1671. Epub 2010 Oct 15. PMID: 20952506; PMCID: PMC3043107. 12: Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Jänne PA. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010 Dec 15;70(24):10038-43. doi: 10.1158/0008-5472.CAN-10-2956. Epub 2010 Oct 28. PMID: 21030459; PMCID: PMC3045808. 13: Li Y, Ye X, Liu J, Zha J, Pei L. Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors. Neoplasia. 2011 Jan;13(1):1-11. doi: 10.1593/neo.101120. PMID: 21245935; PMCID: PMC3022423. 14: Takezawa K, Okamoto I, Nishio K, Jänne PA, Nakagawa K. Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor-induced apoptosis in EML4-ALK-positive lung cancer. Clin Cancer Res. 2011 Apr 15;17(8):2140-8. doi: 10.1158/1078-0432.CCR-10-2798. Epub 2011 Mar 17. PMID: 21415216. 15: Grande E, Bolós MV, Arriola E. Targeting oncogenic ALK: a promising strategy for cancer treatment. Mol Cancer Ther. 2011 Apr;10(4):569-79. doi: 10.1158/1535-7163.MCT-10-0615. Erratum in: Mol Cancer Ther. 2011 Aug;10(8):1529. PMID: 21474455. 16: Cerchietti L, Damm-Welk C, Vater I, Klapper W, Harder L, Pott C, Yang SN, Reiter A, Siebert R, Melnick A, Woessmann W. Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas. PLoS One. 2011 Apr 8;6(4):e18436. doi: 10.1371/journal.pone.0018436. PMID: 21494621; PMCID: PMC3072987. 17: Katayama R, Khan TM, Benes C, Lifshits E, Ebi H, Rivera VM, Shakespeare WC, Iafrate AJ, Engelman JA, Shaw AT. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci U S A. 2011 May 3;108(18):7535-40. doi: 10.1073/pnas.1019559108. Epub 2011 Apr 18. PMID: 21502504; PMCID: PMC3088626. 18: Duijkers FA, Gaal J, Meijerink JP, Admiraal P, Pieters R, de Krijger RR, van Noesel MM. Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels. Cell Oncol (Dordr). 2011 Oct;34(5):409-17. doi: 10.1007/s13402-011-0048-2. Epub 2011 May 31. PMID: 21625996; PMCID: PMC3219872. 19: Sasaki T, Koivunen J, Ogino A, Yanagita M, Nikiforow S, Zheng W, Lathan C, Marcoux JP, Du J, Okuda K, Capelletti M, Shimamura T, Ercan D, Stumpfova M, Xiao Y, Weremowicz S, Butaney M, Heon S, Wilner K, Christensen JG, Eck MJ, Wong KK, Lindeman N, Gray NS, Rodig SJ, Jänne PA. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011 Sep 15;71(18):6051-60. doi: 10.1158/0008-5472.CAN-11-1340. Epub 2011 Jul 26. PMID: 21791641; PMCID: PMC3278914. 20: Schönherr C, Ruuth K, Yamazaki Y, Eriksson T, Christensen J, Palmer RH, Hallberg B. Activating ALK mutations found in neuroblastoma are inhibited by Crizotinib and NVP-TAE684. Biochem J. 2011 Dec 15;440(3):405-13. doi: 10.1042/BJ20101796. PMID: 21838707.