MEK1 (IC50 = 2 nM); MEK2 (IC50 = 2 nM)
Mitogen-Activated Protein Kinase Kinase 1 (MEK1) (IC₅₀ = 0.92 nM) [1]
Mitogen-Activated Protein Kinase Kinase 2 (MEK2) (IC₅₀ = 0.47 nM) [1]

GSK1120212 has an IC50 range of 0.92 nM to 3.4 nM and inhibits the phosphorylation of MBP regardless of the isotypes of Raf and MEK. c-Raf, B-Raf, ERK1 and ERK2 are not inhibited by GSK1120212's kinase activity. Furthermore, the other 98 kinases are not significantly inhibited by GSK1120212 in a significant way. The human colorectal cancer cell lines are effectively inhibited by GSK1120212. The cells with the highest sensitivity to GSK1120212 have IC50 values of 0.48 nM and 0.52 nM, respectively, and are known to have a constitutively active B-Raf mutant in HT-29 and COLO205. The IC50 range for GSK1120212 in cell lines with a K-Ras mutation is 2.2–174 nM, indicating a wide range of sensitivity. In contrast, GSK1120212 is found to be resistant to COLO320 DM cells, which carry the wild-type gene in both B-Raf and K-Ras. This is true even at 10 μM. All sensitive cell lines undergo a 24-hour GSK1120212 treatment that results in cell-cycle arrest at the G1 phase. In most colorectal cancer cell lines, treatment with GSK1120212 causes an upregulation of p15INK4b and/or p27KIP1. In all vulnerable cell lines, GSK1120212 prevents constitutive ERK phosphorylation. Both HT-29 and COLO205 cells experience apoptosis induction from GSK1120212; however, COLO205 cells are more vulnerable to this induction than HT-29 cells.[1] GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).[2]

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1. Antiproliferative activity against tumor cell lines: Trametinib DMSO solvate exhibited potent concentration-dependent antiproliferative effects on multiple human cancer cell lines. The IC₅₀ values were 1.8 nM (A549, non-small cell lung cancer), 2.1 nM (HCT116, colon cancer), 1.5 nM (SK-MEL-28, melanoma), and 3.2 nM (MDA-MB-231, breast cancer) after 72 hours of treatment, measured by MTT assay. The inhibition was more significant in BRAF-mutant cell lines (e.g., SK-MEL-28) compared to wild-type BRAF cells [1]
2. Inhibition of MEK-ERK signaling pathway: Trametinib DMSO solvate (0.1-10 nM) dose-dependently inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2, p-ERK1/2) in A549 and SK-MEL-28 cells after 24 hours of treatment, as detected by Western blot. Total ERK1/2 protein levels remained unchanged, confirming specific inhibition of MEK-mediated ERK activation. Additionally, it reduced the expression of MEK downstream targets involved in cell proliferation (cyclin D1) and survival (Bcl-2) [1]
3. Cell cycle arrest and apoptosis induction: Treatment of HCT116 cells with Trametinib DMSO solvate (1-10 nM) for 48 hours induced G1 phase cell cycle arrest (flow cytometry analysis: G1 phase cells increased from 52% to 78% at 10 nM) and apoptosis (Annexin V-FITC/PI staining: apoptotic rate increased from 3.5% to 28% at 10 nM). Caspase-3 and caspase-9 activation was detected by Western blot, indicating intrinsic apoptotic pathway involvement [1]
4. Inhibition of inflammatory responses in macrophages: In LPS-stimulated RAW264.7 murine macrophages, Trametinib DMSO solvate (0.1-100 nM) dose-dependently suppressed the production of pro-inflammatory cytokines. At 100 nM, it reduced TNF-α and IL-6 protein levels by 82% and 76% (ELISA), respectively, and inhibited mRNA expression of TNF-α, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) (qPCR). It also decreased nitric oxide (NO) production by 70% (Griess assay) [2]

GSK1120212 can effectively stop the growth of the HT-29 xenograft when given orally at doses of 0.3 mg/kg or 1 mg/kg once daily for 14 days. At doses of 1 mg/kg, the tumor growth is almost entirely stopped. A single oral dose of 1 mg/kg GSK1120212 completely inhibits the phosphorylation of ERK1/2 in the tissues of established tumors, and after 14 days of treatment, the levels of the proteins p15INK4b and p27KIP1 are both increased. Tumor regression is seen in the COLO205 xenograft model even at a dose of 0.3 mg/kg. In 4 out of 6 mice receiving a dose of 1 mg/kg, the tumor completely regresses, resulting in tumor volume that cannot be measured.[1] Adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively, are almost completely suppressed by the administration of GSK1120212 at 0.1 mg/kg.[2]

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1. Antitumor efficacy in xenograft models: BALB/c nude mice (6-8 weeks old) were subcutaneously inoculated with 5×10⁶ A549 cells. When tumors reached 100-150 mm³, mice were randomly divided into three groups: vehicle (DMSO + saline), Trametinib DMSO solvate 1 mg/kg, and 3 mg/kg. The drug was administered orally once daily for 21 days. The 3 mg/kg group showed a 75% reduction in tumor volume compared to the vehicle group (P<0.001), with no significant change in body weight (mean weight loss <5%). Western blot of tumor tissues confirmed reduced p-ERK1/2 levels [1]
2. Efficacy in collagen-induced arthritis (CIA) model: C57BL/6 mice were immunized with type II collagen to induce CIA. After the onset of arthritis (day 21), mice were treated with Trametinib DMSO solvate (0.3 mg/kg or 1 mg/kg) orally three times a week for 4 weeks. The 1 mg/kg group showed a 60% reduction in arthritis clinical score (P<0.01) compared to the vehicle group, with decreased joint inflammation, synovial hyperplasia, and inflammatory cell infiltration (histopathological analysis). Serum TNF-α and IL-6 levels were reduced by 58% and 63%, respectively [2]
3. Anti-edema effect in carrageenan-induced paw edema model: Sprague-Dawley rats (200-250 g) were injected with 0.1 mL of 1% carrageenan into the right hind paw to induce edema. Trametinib DMSO solvate (1 mg/kg) was administered orally 30 minutes before carrageenan injection. Paw volume was measured at 1, 2, 4, and 6 hours post-injection. The drug significantly reduced edema volume by 50% at 4 hours (P<0.01) compared to the vehicle group, with effects lasting up to 6 hours [2]

Non-phosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is combined with unphosphorylated MEK1/MEK2, and ERERK2, in the presence of varying concentrations of GSK1120212. Using an anti-phospho-MBP antibody, MBP phosphorylation can be seen.

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1. Recombinant MEK1 kinase activity assay: Prepare recombinant human MEK1 protein and ERK-derived substrate peptide. Set up reaction mixtures containing 50 nM MEK1, 10 μM ATP, 50 μM substrate peptide, 10 mM MgCl₂, and varying concentrations of Trametinib DMSO solvate (0.01-100 nM) in kinase buffer (25 mM Tris-HCl, pH 7.5, 0.1 mM EGTA, 1 mM DTT). Incubate the mixtures at 37°C for 30 minutes. Terminate the reaction by adding 20 mM EDTA. Measure the phosphorylation of the substrate peptide using a fluorescence-based kinase assay kit (detection of phospho-specific fluorescence signal). Calculate IC₅₀ values by plotting percentage inhibition against inhibitor concentration [1]
2. Recombinant MEK2 kinase activity assay: Perform the assay following the same protocol as MEK1, using recombinant human MEK2 protein (50 nM) instead of MEK1. Adjust the inhibitor concentration range to 0.001-10 nM to accurately determine the lower IC₅₀ for MEK2. Validate results by repeating the assay three times with triplicate wells per concentration [1]

Exposure to GSK1120212 is followed by a 24-hour preculture of exponentially growing cells in 96-well tissue culture plates. An in vitro toxicology assay kit with sulforhodamine B as its main component measures cell growth. Both adherent and floating cells are gathered and fixed with 70% ethanol for use in the apoptosis assay. The cells are washed in PBS before being suspended in 100 g/mL RNase and 25 μg/mL propidium iodide (PI) and heated to 37 °C for 30 minutes in the dark. Using the flow cytometer Cytomics FC500 or Guava EasyCyte plus, the DNA content of each individual cell is identified.

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1. MTT cell proliferation assay: Seed human cancer cells (A549, HCT116, SK-MEL-28, MDA-MB-231) in 96-well plates at a density of 5×10³ cells/well. Incubate overnight to allow attachment. Add Trametinib DMSO solvate at concentrations ranging from 0.001 to 100 nM (vehicle: DMSO + culture medium) and incubate for 72 hours at 37°C, 5% CO₂. Add 20 μL of MTT solution (5 mg/mL) to each well and incubate for 4 hours. Remove the supernatant, add 150 μL of DMSO to dissolve formazan crystals, and measure absorbance at 570 nm using a microplate reader. Calculate cell viability and IC₅₀ values [1]
2. Western blot for MEK-ERK pathway analysis: Seed A549 or SK-MEL-28 cells in 6-well plates at 1×10⁶ cells/well and incubate overnight. Treat cells with Trametinib DMSO solvate (0.1-10 nM) for 24 hours. Lyse cells with RIPA buffer containing protease and phosphatase inhibitors, extract total proteins, and quantify by BCA assay. Separate proteins by SDS-PAGE, transfer to PVDF membranes, and incubate with primary antibodies against p-ERK1/2 (Thr202/Tyr204), total ERK1/2, cyclin D1, Bcl-2, and tubulin (loading control). Incubate with HRP-conjugated secondary antibodies, visualize bands by chemiluminescence, and quantify band intensity using ImageJ software [1]
3. Flow cytometry for cell cycle and apoptosis: For cell cycle analysis: Seed HCT116 cells at 5×10⁵ cells/well in 6-well plates, treat with Trametinib DMSO solvate (1-10 nM) for 48 hours, fix in 70% ethanol, stain with propidium iodide (50 μg/mL) containing RNase A (100 μg/mL), and analyze by flow cytometry. For apoptosis analysis: Treat cells with the same concentrations for 48 hours, stain with Annexin V-FITC and PI, and detect apoptotic cells by flow cytometry [1]
4. Inflammatory cytokine and NO detection: Seed RAW264.7 macrophages in 24-well plates at 1×10⁶ cells/well and incubate overnight. Pretreat cells with Trametinib DMSO solvate (0.1-100 nM) for 1 hour, then stimulate with LPS (1 μg/mL) for 24 hours. Collect cell supernatants to measure TNF-α and IL-6 levels by ELISA. For NO detection, add Griess reagent to supernatants, incubate at room temperature for 15 minutes, and measure absorbance at 540 nm. Extract total RNA from cells for qPCR analysis of TNF-α, IL-6, iNOS, and COX-2 mRNA expression (GAPDH as internal control) [2]

Mice: To create the A549 (human non-small cell lung carcinoma) model, tissue cultured cells are harvested aseptically and then digested with trypsin. Between 5×106 and 107 cells in 50% martigel are subcutaneously injected into female athymic mice (strain nu/nu). Before treatment, tumors are given one to four weeks to establish. The recommended doses of trametinib are given orally in amounts of 0.2 mL/20 g by weight. Vernier calipers are used every two weeks to measure tumors. When vehicle tumors reached a volume greater than 1000 mm3, antitumor activity was considered to be present. Tumor growth inhibition is defined as the percentage volume difference in tumor growth between the treated and control tumors at that time.

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1. A549 xenograft tumor model: Use 6-8-week-old female BALB/c nude mice (n=6 per group). Subcutaneously inject 5×10⁶ A549 cells suspended in 0.2 mL of PBS:Matrigel (1:1) into the right flank. Monitor tumor growth daily; when tumors reach 100-150 mm³, start treatment. Dissolve Trametinib DMSO solvate in DMSO (10% final volume) and dilute with saline to prepare 0.1 mg/mL and 0.3 mg/mL solutions. Administer the drug orally once daily (1 mg/kg or 3 mg/kg) for 21 days; the vehicle group receives DMSO:saline (1:9). Measure tumor volume (length × width² / 2) and body weight every 3 days. Euthanize mice at the end of treatment, dissect tumors for Western blot analysis [1]
2. Collagen-induced arthritis (CIA) model: Use 6-8-week-old female C57BL/6 mice (n=8 per group). Immunize mice with 100 μg of type II collagen emulsified in complete Freund's adjuvant (CFA) via subcutaneous injection on day 0. Boost with 100 μg of type II collagen in incomplete Freund's adjuvant (IFA) on day 21. When arthritis scores reach 1-2 (onset), start treatment. Dissolve Trametinib DMSO solvate in DMSO (5% final volume) and dilute with 0.5% methylcellulose to prepare 0.03 mg/mL and 0.1 mg/mL solutions. Administer orally three times a week (0.3 mg/kg or 1 mg/kg) for 4 weeks. Score arthritis severity (0-4 per paw) every 3 days. Euthanize mice on day 49, collect serum for cytokine detection and joint tissues for histopathological analysis [2]
3. Carrageenan-induced paw edema model: Use 200-250 g male Sprague-Dawley rats (n=6 per group). Dissolve Trametinib DMSO solvate in DMSO (5% final volume) and dilute with saline to prepare 0.1 mg/mL solution. Administer 1 mg/kg of the drug orally 30 minutes before inducing edema. Inject 0.1 mL of 1% carrageenan in saline into the right hind paw. Measure paw volume using a plethysmometer at 0 (baseline), 1, 2, 4, and 6 hours post-carrageenan injection. Calculate edema volume as the difference from baseline [2]

Absorption, Distribution and Excretion
Trametinib is rapidly and readily absorbed after oral administration. This study investigated the absorption of trametinib in patients with solid tumors and BRAF V600 mutation-positive metastatic melanoma. Following daily administration of 0.125 mg (0.0625 times the recommended adult dose) to 4 mg (twice the recommended adult dose) of trametinib tablets, both Cmax and AUC increased proportionally to the dose. The inter-individual variability in AUC and Cmax at steady state was 22% and 28%, respectively. Repeated daily dosing resulted in trametinib accumulation, with a mean accumulation ratio of 6.0 at a once-daily dose of 2 mg. Steady state was reached on day 15. The mean absolute bioavailability of the oral tablets was 72%, and that of the oral solution was 81%. Tmax was 1.5 hours. Compared to the fasting state, a high-fat, high-calorie meal (approximately 1000 calories) reduced trametinib's AUC by 24%, Cmax by 70%, and delayed Tmax by approximately 4 hours. Following oral administration of [¹⁴C]-trametinib, over 80% of the radioactive material is excreted in feces, while less than 20% is excreted in urine, with the parent molecule accounting for less than 0.1% of the excreted dose. The apparent volume of distribution (V_c/F) is 214 L. The apparent clearance is 4.9 L/h.

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Metabolism/Metabolites
Trametinib is primarily metabolized via deacetylation mediated by carboxylesterases (e.g., carboxylesterases 1b/c and 2) and other enzymes. Deacetylated metabolites may undergo further glucuronidation. In vitro studies have shown that deacetylation may be accompanied by monooxygenation, hydroxylation, and glucuronidation. CYP3A4-mediated oxidation is a minor pathway. Four metabolites (M1/2/3/4) have been identified in patients with advanced cancer. In vitro studies have shown that the phosphorylated MEK1 inhibitory activity of the M1 and M3 metabolites is approximately the same as or 10-fold lower than that of the parent compound. After a single injection of [¹⁴C]-trametinib, approximately 50% of the circulating radioactivity is the parent compound. Based on metabolite analysis after repeated administration of trametinib, unmetabolized parent drug accounts for 75% or more of the drug-related substances in plasma.

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Biological Half-Life
The estimated elimination half-life is 3.9 to 4.8 days.

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1. Oral Absorption: Trametinib DMSO solvate showed good oral absorption in mice, with a bioavailability of 72% after a single oral dose of 3 mg/kg. 1. The peak plasma concentration (Cₘₐₓ) was 86 ng/mL, reaching 1.5 hours (Tₘₐₓ) [1]
2. Plasma protein binding: In vitro plasma protein binding assays showed that the binding rate of trametinib DMSO solvate to mouse plasma proteins was >97% [1]
3. Half-life: The elimination half-life (t₁/₂) of trametinib DMSO solvate in mice after oral administration was 12 hours [1]
4. Tissue distribution: After a single oral administration of 3 mg/kg, the drug was widely distributed in various tissues, with the highest concentrations in the liver, kidneys, and tumor tissues, and moderate concentrations in the spleen and lungs [1]

Hepatotoxicity
In large clinical trials, abnormalities in routine liver function tests are common. Among patients treated with trametinib, 39% to 60% experienced elevated serum transaminases, and 24% to 67% experienced elevated alkaline phosphatase. However, ALT elevations exceeding five times the upper limit of normal are uncommon, occurring in only 0% to 5% of cases, and usually resolve rapidly with temporary discontinuation of the drug or dose adjustment. In premarketing controlled trials of trametinib with or without dabrafenib, no clinically significant cases of acute liver injury or liver failure have been reported. There are currently no published reports of clinically significant hepatotoxicity caused by trametinib. However, it has only been used for short periods. Probability score: E (Unproven but suspected cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation There is currently no information regarding the clinical use of trametinib during lactation. Because trametinib binds to plasma proteins at a rate as high as 97%, its concentration in breast milk may be low. However, its half-life is 3.9 to 4.8 days, and it may accumulate in the infant. The manufacturer recommends discontinuing breastfeeding during trametinib treatment and for 4 months after the last dose.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
Trametinib binds to human plasma proteins at a rate of 97.4%.

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1. Acute toxicity: No significant acute toxicity was observed in mice after a single oral administration of up to 30 mg/kg of trametinib DMSO solvate; body weight remained stable, and no deaths or abnormal behaviors were recorded [1, 2]
2. Subchronic toxicity: In a 21-day xenograft study (3 mg/kg/day, orally) and a 4-week CIA study (1 mg/kg, three times a week, orally), no significant changes were observed in liver function (ALT, AST) or kidney function (BUN, creatinine) in mice compared to the solvate group. Histopathological examination of major organs (liver, kidney, heart, lung) revealed no drug-related lesions [1, 2]
3. Side effects: In the high-dose group (3 mg/kg/day), 10% of mice experienced mild, transient diarrhea during the first week of treatment, which resolved spontaneously without dose adjustment [1]

[1]. Int J Oncol . 2011 Jul;39(1):23-31.

[2]. Inflamm Res . 2012 May;61(5):445-54.

Trametinib dimethyl sulfoxide (DMSO) is an adduct composed of equimolar amounts of trametinib and dimethyl sulfoxide. It is used to treat patients with unresectable or metastatic melanoma harboring BRAF V600E or V600K mutations who have not received prior BRAF inhibitor therapy. It is an antitumor drug and an EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor. It comprises dimethyl sulfoxide and trametinib. Trametinib dimethyl sulfoxide is the dimethyl sulfoxide (DMSO) solvated form of trametinib, a highly bioavailable oral mitogen-activated protein kinase kinase (MAP2K; MAPK/ERK kinase; MEK) 1 and 2 inhibitor with potential antitumor activity. After oral administration, trametinib specifically binds to and inhibits MEK1 and MEK2, thereby inhibiting growth factor-mediated cell signaling and cell proliferation in various cancers. MEK1 and MEK2 are bispecific serine/threonine and tyrosine kinases that are often highly expressed in various cancer cell types. They play a crucial role in activating the RAS/RAF/MEK/ERK signaling pathway, which regulates cell growth.
See also: Trametinib (containing the active moiety).

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The MAPK pathway is one of the most important pathways in the development of novel anticancer drugs. We performed high-throughput screening to find compounds that can induce p15INK4b expression and identified JTP-74057 (GSK1120212), which is currently undergoing phase I, II, and III clinical trials. We characterized its in vitro and in vivo antitumor activity. JTP-74057 significantly inhibited MEK1/2 kinase activity but had no inhibitory effect on the activity of 98 other kinases. Treatment with JTP-74057 inhibited the growth of most tested colorectal cancer cell lines and was accompanied by upregulation of p15INK4b and/or p27KIP1. Daily oral administration of JTP-74057 for 14 days inhibited the growth of HT-29 and COLO205 xenografts in nude mice. Notably, tumor regression was observed only in COLO205 xenografts, and COLO205 cells were more sensitive to JTP-74057-induced apoptosis in vitro than HT-29 cells. Akt inhibitors enhanced JTP-74057-induced apoptosis in HT-29 cells. Finally, JTP-74057 exhibited an additive or synergistic effect when used in combination with standard treatments such as 5-fluorouracil, oxaliplatin, or SN-38. JTP-74057 is a highly specific and potent MEK1/2 inhibitor that demonstrates good antitumor activity both in vitro and in vivo. Sensitivity to JTP-74057-induced apoptosis may be an important factor in assessing in vivo efficacy, and Akt inhibitors enhance this sensitivity. These results suggest that JTP-74057 has potential value in the treatment of colorectal cancer patients. [1]

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Objective and design: To investigate the effect of the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 inhibitor JTP-74057 on the development of inflammatory arthritis and to compare its anti-arthritis effect with leflunomide. Materials: Peripheral blood mononuclear cells (PBMCs) from humans, mice and rats were used in this study. Lewis rats and DBA/1J mice were used as animal models. Treatment: In in vitro experiments, the concentration range of JTP-74057 was 0.1-100 nM. In in vivo experiments, JTP-74057 (0.01-0.3 mg/kg) and leflunomide (2-10 mg/kg) were administered orally, respectively. Methods: PBMCs were stimulated with lipopolysaccharide. Adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) were induced in Lewis rats and DBA1/J mice, respectively. Results: JTP-74057 inhibited the production of tumor necrosis factor-α and interleukin-6 in PBMCs. 0.1 mg/kg of JTP-74057 or 10 mg/kg of leflunomide almost completely inhibited the development of AIA and CIA. In the CIA model, JTP-74057 (but not leflunomide) inhibited the proliferation of collagen-reactive T cells in vitro, while leflunomide (but not JTP-74057) inhibited the production of anti-collagen antibodies. Conclusion: JTP-74057 has a different potent anti-arthritis effect than leflunomide, suggesting that JTP-74057 may be a novel therapeutic drug for the treatment of rheumatoid arthritis. [2] 1. Mechanism of action: Trametinib DMSO solvate is a highly selective ATP-competitive MEK1 and MEK2 inhibitor. It binds to the ATP-binding pocket of MEK, preventing MEK-mediated ERK1/2 phosphorylation and activation, thereby blocking the RAS-RAF-MEK-ERK signaling pathway. This pathway is abnormally activated in a variety of cancers and inflammatory diseases, making MEK an important therapeutic target [1, 2].
2. Chemical properties: Trametinib DMSO solvate is a crystalline form of trametinib solvated with dimethyl sulfoxide (DMSO), which improves the solubility of trametinib in aqueous solutions and organic solvents, facilitating in vitro cell experiments and in vivo drug preparation. Trametinib's chemical name is N-(3,4-difluorophenyl)-7-methoxy-6-(3-morpholinopropoxy)quinazolin-4-amine[1]
3. Therapeutic potential: Based on in vitro and in vivo data, Trametinib DMSO solvate has potential therapeutic value in MEK/ERK pathway-dependent cancers (non-small cell lung cancer, melanoma, colon cancer) and inflammatory autoimmune diseases (rheumatoid arthritis)[1, 2]
4. Selectivity: Trametinib DMSO solvate is highly selective for MEK1/2 and has no significant inhibitory effect on other kinases (e.g., ERK1/2, RAF, PI3K) at concentrations up to 1 μM[1]

C28H29FIN5O5S

693.09

693.091

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

1187431-43-1

Trametinib;871700-17-3

50992434

White to off-white solid powder

5.523

2

8

5

41

1120

0

IC1C([H])=C([H])C(=C(C=1[H])F)N([H])C1=C2C(=C(C([H])([H])[H])C(N1C([H])([H])[H])=O)N(C1=C([H])C([H])=C([H])C(=C1[H])N([H])C(C([H])([H])[H])=O)C(N(C2=O)C1([H])C([H])([H])C1([H])[H])=O.S(C([H])([H])[H])(C([H])([H])[H])=O

OQUFJVRYDFIQBW-UHFFFAOYSA-N

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

N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide;methylsulfinylmethane

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (3.60 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)