Trametinib DMSO solvate | CAS#1187431-43-1 | MEK1/MEK2 inhibitor

MedKoo Cat#: 123211 | Name: Trametinib DMSO solvate

Description:

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

Trametinib DMSO solvate is a solvated form of trametinib at 1:1 molar ratio of trametinib to dimethyl sulfoxide. Trametinib, also known as GSK1120212, GSK212 or JTP74057, is an approved and new targeted drug for the treatment of melanoma. It is a powerful and selective MEK1/MEK2 inhibitor which can effectively prevent cancer cell proliferating and can induce cell apoptosis, and increase the life of patients.

Chemical Structure

Trametinib DMSO solvate

CAS#1187431-43-1 (DMSO)

Theoretical Analysis

MedKoo Cat#: 123211

Name: Trametinib DMSO solvate

CAS#: 1187431-43-1 (DMSO)

Chemical Formula: C28H29FIN5O5S

Exact Mass: 0.0000

Molecular Weight: 693.09

Elemental Analysis: C, 48.49; H, 4.21; F, 2.74; I, 18.30; N, 10.10; O, 11.53; S, 4.62

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 250.00	Ready to ship
200mg	USD 450.00	Ready to ship
500mg	USD 1,015.00	Ready to ship
1g	USD 1,825.00	Ready to Ship

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Related CAS #

871700-17-3 1187431-43-1 (DMSO)

Synonym

Trametinib DMSO solvate; Trametinib dimethyl sulfoxide; GSK-1120212 DMSO solvate;Trametinib;JTP-74057; JTP 74057; JTP74057; GSK-1120212;GSK1120212;GSK 1120212.

IUPAC/Chemical Name

N-(3-(3-cyclopropyl-5-((2-fluoro-4-iodophenyl)amino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide compound with (methylsulfinyl)methane (1:1)

InChi Key

OQUFJVRYDFIQBW-UHFFFAOYSA-N

InChi Code

InChI=1S/C26H23FIN5O4.C2H6OS/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34;1-4(2)3/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34);1-2H3

SMILES Code

CC1=C2C(C(N(C3CC3)C(N2C4=CC(NC(C)=O)=CC=C4)=O)=O)=C(NC5=C(F)C=C(I)C=C5)N(C)C1=O.CS(C)=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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60218

QC Data

View QC data: current batch, Lot#TZC60218

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Trametinib (GSK1120212; JTP-74057) is an MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM.

In vitro activity:

Interestingly, several IAV (Influenza A virus)-induced cytokines were reduced on mRNA level in presence of Trametinib (Fig. 4A and B). The expression of IFNβ and the interferon stimulated gene (ISG) MxA was only found to be reduced by Trametinib in infected cells (Fig. 4A), but not strongly affected in vRNA-transfected cells (Fig. 4C). The results indicate that the cellular IFN response is not directly limited by Trametinib. Rather it seems to be primarily indirectly affected by reduced viral replication than being directly caused by deregulation of the Raf/MEK/ERK signaling cascade. Indeed, expression of IFNβ and MxA are not yet described to be directly regulated by the Raf/MEK/ERK signaling cascade. Considering Trametinib as antiviral drug it is beneficial that Trametinib does not directly alter the IFN response which is an important arm of cellular antiviral defense. A clearly decreased induction by Trametinib was also detectable for IL6, CCL5 and CXCL10 mRNA expression, which were induced by infection with PR8M/H1N1 (Fig. 4B). Reference: Mol Cancer Ther. 2016 Jan;15(1):172-83. https://pubmed.ncbi.nlm.nih.gov/29990517/

In vivo activity:

This study examined the mechanism by which trametinib impacts T-cell subpopulations after islet transplantation. T-cell subpopulations isolated from the liver and spleen of recipient mice on day 7, which were treated with vehicle or with 0.1 or 0.3 mg/kg trametinib, were analyzed by flow cytometry (n = 3/group). The ratio of CD8+ T cells to CD4+ T cells in the liver of trametinib-treated mice tended to be lower than that in the vehicle-treated group (Figure 4A; 1-way ANOVA; P = 0.26), indicating that trametinib suppresses infiltration of the liver by CD8+ T cells. Among the different CD4+ T-cell subpopulations, trametinib increased the percentage of naive T cells (CD62L+CD44–) in the liver in a dose-dependent manner; it also reduced the percentage of effector memory T cells (CD62L-CD44+) in the liver and spleen (Figure 4B; 1-way ANOVA; all P < 0.05). By contrast, trametinib had no effect on CD8+ T-cell subpopulations in the liver or spleen (Figure 4C). These results suggest that (at least in vivo) trametinib mainly suppresses functional differentiation of CD4+ naive T cells. Reference: Transplant Direct. 2020 Sep; 6(9): e591. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423917/

	Solvent	mg/mL	mM
Solubility
	DMSO	59.5	85.85

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 693.09 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. Itamura H, Shindo T, Tawara I, Kubota Y, Kariya R, Okada S, Komanduri KV, Kimura S. The MEK inhibitor trametinib separates murine graft-versus-host disease from graft-versus-tumor effects. JCI Insight. 2016 Jul 7;1(10):e86331. doi: 10.1172/jci.insight.86331. PMID: 27699218; PMCID: PMC5033881. 2. Bridgeman VL, Wan E, Foo S, Nathan MR, Welti JC, Frentzas S, Vermeulen PB, Preece N, Springer CJ, Powles T, Nathan PD, Larkin J, Gore M, Vasudev NS, Reynolds AR. Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma. Mol Cancer Ther. 2016 Jan;15(1):172-83. doi: 10.1158/1535-7163.MCT-15-0170. Epub 2015 Oct 20. PMID: 26487278. 3. Tada S, Anazawa T, Shindo T, Yamane K, Inoguchi K, Fujimoto N, Nagai K, Masui T, Okajima H, Takaori K, Sumi S, Uemoto S. The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation. Transplant Direct. 2020 Aug 12;6(9):e591. doi: 10.1097/TXD.0000000000001045. PMID: 32851124; PMCID: PMC7423917.

In vitro protocol:

In vivo protocol:

1. Tada S, Anazawa T, Shindo T, Yamane K, Inoguchi K, Fujimoto N, Nagai K, Masui T, Okajima H, Takaori K, Sumi S, Uemoto S. The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation. Transplant Direct. 2020 Aug 12;6(9):e591. doi: 10.1097/TXD.0000000000001045. PMID: 32851124; PMCID: PMC7423917. 2. Bridgeman VL, Wan E, Foo S, Nathan MR, Welti JC, Frentzas S, Vermeulen PB, Preece N, Springer CJ, Powles T, Nathan PD, Larkin J, Gore M, Vasudev NS, Reynolds AR. Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma. Mol Cancer Ther. 2016 Jan;15(1):172-83. doi: 10.1158/1535-7163.MCT-15-0170. Epub 2015 Oct 20. PMID: 26487278.

1: Kasuga A, Nakagawa K, Nagashima F, Shimizu T, Naruge D, Nishina S, Kitamura H, Kurata T, Takasu A, Fujisaka Y, Okamoto W, Nishimura Y, Mukaiyama A, Matsushita H, Furuse J. A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. Invest New Drugs. 2015 Aug 12. [Epub ahead of print] PubMed PMID: 26259955. 2: Giurcaneanu C, Nitipir C, Popa LG, Forsea AM, Popescu I, Bumbacea RS. Evolution of Melanocytic Nevi under Vemurafenib, Followed by Combination Therapy with Dabrafenib and Trametinib for Metastatic Melanoma. Acta Dermatovenerol Croat. 2015 Jul;23(2):87-95. Review. PubMed PMID: 26228819. 3: Modak S, Asante-Korang A, Steinherz LJ, Grana N. Trametinib-induced Left Ventricular Dysfunction in a Child With Relapsed Neuroblastoma. J Pediatr Hematol Oncol. 2015 Aug;37(6):e381-3. doi: 10.1097/MPH.0000000000000364. PubMed PMID: 26181424. 4: Schick U, Kyula J, Barker H, Patel R, Zaidi S, Gregory C, Hafsi H, Roulstone V, Deutsch E, McLaughlin M, Harrington K. Trametinib radiosensitises RAS- and BRAF-mutated melanoma by perturbing cell cycle and inducing senescence. Radiother Oncol. 2015 Jul 8. pii: S0167-8140(15)00323-0. doi: 10.1016/j.radonc.2015.06.026. [Epub ahead of print] PubMed PMID: 26163092. 5: Chopra N, Nathan PD. Trametinib in metastatic melanoma. Expert Rev Anticancer Ther. 2015;15(7):749-60. doi: 10.1586/14737140.2015.1060127. PubMed PMID: 26107021. 6: Melanoma: Dabrafenib and trametinib improve overall survival. Nat Rev Clin Oncol. 2015 Sep;12(9):502. doi: 10.1038/nrclinonc.2015.114. Epub 2015 Jun 23. PubMed PMID: 26099986. 7: Draganova D, Kerger J, Caspers L, Willermain F. Severe bilateral panuveitis during melanoma treatment by Dabrafenib and Trametinib. J Ophthalmic Inflamm Infect. 2015 Jun 9;5:17. doi: 10.1186/s12348-015-0049-9. eCollection 2015. PubMed PMID: 26078801; PubMed Central PMCID: PMC4460117. 8: Menzies AM, Yeh I, Botton T, Bastian BC, Scolyer RA, Long GV. Clinical activity of the MEK inhibitor trametinib in metastatic melanoma containing BRAF kinase fusion. Pigment Cell Melanoma Res. 2015 Sep;28(5):607-10. doi: 10.1111/pcmr.12388. Epub 2015 Jul 3. PubMed PMID: 26072686; PubMed Central PMCID: PMC4539279. 9: Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JB, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Swann S, Legos JJ, Jin F, Mookerjee B, Flaherty K. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015 Aug 1;386(9992):444-51. doi: 10.1016/S0140-6736(15)60898-4. Epub 2015 May 31. PubMed PMID: 26037941. 10: Minor DR, Puzanov I, Callahan MK, Hug BA, Hoos A. Severe gastrointestinal toxicity with administration of trametinib in combination with dabrafenib and ipilimumab. Pigment Cell Melanoma Res. 2015 Sep;28(5):611-2. doi: 10.1111/pcmr.12383. Epub 2015 Jun 23. PubMed PMID: 25996827. 11: Escandell I, Cabezas M, Martín JM, Terradez L, Pinazo MI. Effective treatment with Dabrafenib and Trametinib for a BRAF-mutated metastatic dedifferentiated malignant spindle cell neoplasm. J Eur Acad Dermatol Venereol. 2015 Apr 27. doi: 10.1111/jdv.13155. [Epub ahead of print] PubMed PMID: 25917403. 12: Qiu JG, Zhang YJ, Li Y, Zhao JM, Zhang WJ, Jiang QW, Mei XL, Xue YQ, Qin WM, Yang Y, Zheng DW, Chen Y, Wei MN, Shi Z. Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter. Oncotarget. 2015 Jun 20;6(17):15494-509. PubMed PMID: 25915534. 13: Fujishita T, Kajino-Sakamoto R, Kojima Y, Taketo MM, Aoki M. Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation in Apc(Δ716) mice involves stromal COX-2. Cancer Sci. 2015 Jun;106(6):692-9. doi: 10.1111/cas.12670. Epub 2015 May 1. PubMed PMID: 25855137. 14: Rissmann R, Hessel MH, Cohen AF. Vemurafenib/dabrafenib and trametinib. Br J Clin Pharmacol. 2015 Apr 6. doi: 10.1111/bcp.12651. [Epub ahead of print] PubMed PMID: 25847075. 15: Thota R, Johnson DB, Sosman JA. Trametinib in the treatment of melanoma. Expert Opin Biol Ther. 2015 May;15(5):735-47. doi: 10.1517/14712598.2015.1026323. Epub 2015 Mar 26. PubMed PMID: 25812921. 16: Schadendorf D, Amonkar MM, Stroyakovskiy D, Levchenko E, Gogas H, de Braud F, Grob JJ, Bondarenko I, Garbe C, Lebbe C, Larkin J, Chiarion-Sileni V, Millward M, Arance A, Mandalà M, Flaherty KT, Nathan P, Ribas A, Robert C, Casey M, DeMarini DJ, Irani JG, Aktan G, Long GV. Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma. Eur J Cancer. 2015 May;51(7):833-40. doi: 10.1016/j.ejca.2015.03.004. Epub 2015 Mar 17. PubMed PMID: 25794603. 17: Blumenschein GR Jr, Smit EF, Planchard D, Kim DW, Cadranel J, De Pas T, Dunphy F, Udud K, Ahn MJ, Hanna NH, Kim JH, Mazieres J, Kim SW, Baas P, Rappold E, Redhu S, Puski A, Wu FS, Jänne PA. A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC)†. Ann Oncol. 2015 May;26(5):894-901. doi: 10.1093/annonc/mdv072. Epub 2015 Feb 26. PubMed PMID: 25722381. 18: Joshi M, Rice SJ, Liu X, Miller B, Belani CP. Trametinib with or without vemurafenib in BRAF mutated non-small cell lung cancer. PLoS One. 2015 Feb 23;10(2):e0118210. doi: 10.1371/journal.pone.0118210. eCollection 2015. PubMed PMID: 25706985; PubMed Central PMCID: PMC4338247. 19: Du SL, Yuan X, Zhan S, Tang LJ, Tong CY. Trametinib, a novel MEK kinase inhibitor, suppresses lipopolysaccharide-induced tumor necrosis factor (TNF)-α production and endotoxin shock. Biochem Biophys Res Commun. 2015 Mar 13;458(3):667-73. doi: 10.1016/j.bbrc.2015.01.160. Epub 2015 Feb 13. PubMed PMID: 25684183. 20: Mas C, Boda B, CaulFuty M, Huang S, Wiszniewski L, Constant S. Antitumour efficacy of the selumetinib and trametinib MEK inhibitors in a combined human airway-tumour-stroma lung cancer model. J Biotechnol. 2015 Jul 10;205:111-9. doi: 10.1016/j.jbiotec.2015.01.012. Epub 2015 Jan 20. PubMed PMID: 25615947.