| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
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| Targets |
PRMT5/MTA complex (IC50 = 7070 nM)
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|---|---|
| ln Vitro |
In MTAP deletion HCT116 dividing wild-type cells, MRTX-1719 (10 days) suppresses PRMT5 activity with an IC50 of 8 nM [1]. In HCT116 cells lacking MTAP, the IC50 value of MRTX1719 (10 days) is 12 nM, but in HCT116 cells with wild-type phenotype, it is 890 nM [1].
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| ln Vivo |
MRTX1719 (12.5-100 mg/kg/day, face, 21 days) inhibits tumor growth in Lu-99 orthotopic xenografts [2]. Pharmacokinetic analysis [2] Model Route Dose (mg/kg) Cltotal ( mL/min/kg) Vdss (L/kg) t1/2 (h) CD-1 mice. iv 3 83 6.3 1.5 Beagle dog iv 2 14 3.4 4.8 Cynomolgus monkey iv 2 15 2.3 6.1 Model route dose (mg/kg) Cmax (ug/mL) AUCinf (h*ug/mL) F (%) CD-1 tiny mouse. po 30 1.16 4.85 80 Beagle dog po 10 1.40 7.47 59 Cynomolgus monkey po 10 / / 41
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| References |
[1]. Lars D Engstrom, et al. MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP deleted cancer. Cancer Discov. 2023 Aug 8;CD-23-0669.
[1]. Mta-cooperative prmt5 inhibitors. WO2021050915A1. |
| Additional Infomation |
PRMT5-MTA Inhibitor MRTX1719 is an orally bioavailable inhibitor of the protein arginine methyltransferase 5 (PRMT5)-methylthioadenosine (MTA) complex, with potential antineoplastic activity. Upon oral administration, PRMT5-MTA inhibitor MRTX1719 selectively binds to the PRMT5-MTA complex that is elevated in methylthioadenosine phosphoylase (MTAP)-deleted cancer cells, thereby specifically inhibiting the function of PRMT5 solely within MTAP-deleted cancer cells and not in normal, healthy cells. By inhibiting the methyltransferase activity of PRMT5, levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 are decreased. This modulates the expression of genes involved in several cellular processes, including cellular proliferation. This may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation, which may lead to decreased growth of rapidly proliferating cancer cells. MRTX1719 also causes dysregulated RNA splicing and decreased pRb. Together, this decreases proliferation and increases apoptosis specifically in MTAP-deleted cancer cells. PRMT5, a type II methyltransferase that catalyzes the formation of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on histones and a variety of other protein substrates involved in signal transduction and cellular transcription, is essential for the viability of cancer and normal cells. It is overexpressed in several neoplasms. Elevated levels are associated with decreased patient survival. MTAP is deleted in certain cancer cells leading to an accumulation of the metabolite MTA; MTA binds to and partially inhibits the activity of PRMT5.
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| Molecular Formula |
C23H18CLFN6O2
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|---|---|
| Molecular Weight |
464.88
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| Exact Mass |
464.116
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| Elemental Analysis |
C, 59.42; H, 3.90; Cl, 7.63; F, 4.09; N, 18.08; O, 6.88
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| CAS # |
2630904-44-6
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| Related CAS # |
MRTX-1719;2630904-45-7
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| PubChem CID |
156151242
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| Appearance |
Typically exists as white to off-white solids at room temperature
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| LogP |
2.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
846
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BZKIOORWZAXIBA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H18ClFN6O2/c1-31-22(20-15(8-26)19(33-12-3-4-12)7-17(24)21(20)25)16(10-28-31)11-2-5-13-14(6-11)18(9-27)29-30-23(13)32/h2,5-7,10,12H,3-4,9,27H2,1H3,(H,30,32)
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| Chemical Name |
2-[4-[4-(aminomethyl)-1-oxo-2H-phthalazin-6-yl]-2-methylpyrazol-3-yl]-4-chloro-6-cyclopropyloxy-3-fluorobenzonitrile
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| Synonyms |
(S)-MRTX1719
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1511 mL | 10.7555 mL | 21.5109 mL | |
| 5 mM | 0.4302 mL | 2.1511 mL | 4.3022 mL | |
| 10 mM | 0.2151 mL | 1.0755 mL | 2.1511 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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