MRTX9768 hydrochloride

Name: MRTX9768 hydrochloride
Brand: MedChemExpress
SKU: HY-138684A
Rating: 4.5 (1 reviews)

Cat. No.: HY-138684A Purity: 99.68%: FAQs
Data Sheet SDS COA Handling Instructions

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MRTX9768 hydrochloride is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor.

For research use only. We do not sell to patients.

MRTX9768 hydrochloride Chemical Structure

Size	Price	Stock	Quantity
5 mg	USD 860	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 1380	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 2760	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 4450	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 7100	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Customer Review

Based on 1 publication(s) in Google Scholar

Other Forms of MRTX9768 hydrochloride:

MRTX9768 In-stock

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•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Histone Methyltransferase Isoform Specific Products:

View All Isoforms

EZH1 EZH2 DOT1L SMYD2 SMYD3 SUV39H2/KMT1B EHMT2/G9a/KMT1C EHMT1/GLP/KMT1D SETDB1/KMT2G SETD2/KMT3A SETD7/KMT7 SETD8/KMT5A PRMT1 PRMT3 PRMT4 PRMT5 PRMT6 PRMT7 PRMT8

Biological Activity
Purity & Documentation
References
Customer Review

Description

MRTX9768 hydrochloride is a potent, selective, orally active, first-in-class PRMT5-MTA complex inhibitor^[1].

IC₅₀ & Target

PRMT5•MTA^[1]

In Vitro

MRTX9768 inhibits SDMA and cell proliferation in HCT116 MTAP-del cells (SDMA IC₅₀ 3 nM; prolif. IC₅₀ 11 nM) with marked selectivity over HCT116 MTAP-WT cells (SDMA IC₅₀ 544 nM; prolif. IC₅₀ 861 nM)^[1].
MRTX9768 (0-250 nM) results in LU99 SDMA inhibition maintaining after 3-hr drug treatment followed by 4-day washout (exhibiting tight binding and prolonged PRMT5•MTA occupancy)^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

In xenograft studies, oral administration of MRTX9768 demonstrates dose-dependent inhibition of SDMA in MTAP-del tumors, with less SDMA modulation observed in bone marrow^[1].
MRTX9768 selectively targets MTAP/CDKN2A-deleted tumors (such as glioblastoma)^[1]^[2].
MRTX9768 (PO dose 30 mg/kg in CD-1 mouse and beagle dog, 10 mg/kg in cynomolgus monkey) has a favorable ADME profile (>50% bioavailability in mice and dogs, moderate to high clearance, No changes in RBC parameters when administered well above efficacious concentrations (1000 mg/kg))^[3].
MRTX9768 (100 mg/kg, orally, BID, 6/21 days) results in SDMA inhibition maintaining 3 days after dosing is stopped^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

460.89

Formula

C₂₄H₁₈ClFN₆O

Appearance

Solid

Color

White to off-white

SMILES

N#CC1=C(C2=C(C3=CC4=C(C(NN=C4CN)=O)C=C3)C=NN2C)C(F)=CC5=C1C=CC=C5.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

Solvent & Solubility

In Vitro:

H₂O : 40 mg/mL (86.79 mM; Need ultrasonic)

DMSO : 19 mg/mL (41.22 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.1697 mL	10.8486 mL	21.6971 mL
5 mM	0.4339 mL	2.1697 mL	4.3394 mL
10 mM	0.2170 mL	1.0849 mL	2.1697 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 4.5 mg/mL (9.76 mM); Clear solution

This protocol yields a clear solution of ≥ 4.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (45.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 4.5 mg/mL (9.76 mM); Clear solution

This protocol yields a clear solution of ≥ 4.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (45.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 4.5 mg/mL (9.76 mM); Clear solution

This protocol yields a clear solution of ≥ 4.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (45.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.68%

Select Batch:

Data Sheet (281 KB) SDS (251 KB)

COA (258 KB) HNMR (260 KB) RP-HPLC (660 KB) LCMS (131 KB)

Handling Instructions (2659 KB)

References

[1]. Christopher R. Smith, et al. Abstract LB003: Fragment based discovery of MRTX9768, a synthetic lethal-based inhibitor designed to bind the PRMT5-MTA complex and selectively target MTAP/CDKN2A-deleted tumors. AACR Annual Meeting 2021; April 10-15, 2021 and

[2]. Yingqing Chen, et al. Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms. Biomed Pharmacother. 2021 Oct 4;144:112252. [Content Brief]

[3]. Matthew A. Marx, et al. Fragment-based discovery of MRTX9768, a synthetic lethal- based inhibitor designed to bind the PRMT5•MTA complex and selectively target MTAPDEL tumors. AACR ANNUAL MEETING 2021:APRIL 10-15, 2021 AND MAY 17-21, 2021.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO / H₂O	1 mM	2.1697 mL	10.8486 mL	21.6972 mL	54.2429 mL
	5 mM	0.4339 mL	2.1697 mL	4.3394 mL	10.8486 mL
	10 mM	0.2170 mL	1.0849 mL	2.1697 mL	5.4243 mL
	15 mM	0.1446 mL	0.7232 mL	1.4465 mL	3.6162 mL
	20 mM	0.1085 mL	0.5424 mL	1.0849 mL	2.7121 mL
	25 mM	0.0868 mL	0.4339 mL	0.8679 mL	2.1697 mL
	30 mM	0.0723 mL	0.3616 mL	0.7232 mL	1.8081 mL
	40 mM	0.0542 mL	0.2712 mL	0.5424 mL	1.3561 mL
H₂O	50 mM	0.0434 mL	0.2170 mL	0.4339 mL	1.0849 mL
	60 mM	0.0362 mL	0.1808 mL	0.3616 mL	0.9040 mL
	80 mM	0.0271 mL	0.1356 mL	0.2712 mL	0.6780 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.