MRX-2843 (UNC2371)

Alias: MRX-2843; UNC 2371; UNC2371A; UNC-2371; UNC-2371A; MRX2843; UNC2371; UNC 2371A; MRX 2843

Cat No.:V5202 Purity: ≥98%

COA Product Data Instructions for use SDS

MRX-2843 (also known as MRX2843; UNC-2371) is a novel, potent and orally bioactivesmall-molecule inhibitor of MERTK and FLT3 with anticancer activity.

MRX-2843 (UNC2371) Chemical Structure CAS No.: 1429882-07-4
Product category: FLT3

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

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Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

MRX-2843 (also known as MRX2843; UNC-2371) is a novel, potent and orally bioactive small-molecule inhibitor of MERTK and FLT3 with anticancer activity. In cases of acute myeloid leukemia, MRX-2843 overcomes FLT3 mutations that confer resistance. A novel approach to treating patients with wtEGFR NSCLC is to combine MRX-2843 with an irreversible EGFR TKI. With a broad therapeutic window compared to normal human cord blood cells, MRX-2843 treatment induces apoptosis and inhibits colony formation in AML cell lines and primary patient samples expressing MERTK and/or FLT3-ITD.

Biological Activity I Assay Protocols (From Reference)

Targets

FLT3 (IC50 = 0.64 nM); MERTK (IC50 = 1.3 nM)

ln Vitro

MRX-2843 treatment induces a dose-dependent suppression of MERTK phosphorylation in the Kasumi-1 cell line. As little as 10 nM shows signs of decreased phosphorylation, and between 100 and 300 nM almost entirely abolishes MERTK activation. In a similar vein, MRX-2843 treatment of Kasumi-1 cells results in downstream signaling pathways crucial for tumor cell survival and proliferation being inhibited. With an IC50 of 143.5±14.1 nM, MRX-2843 treatment causes a decrease in relative cell numbers, suggesting that it significantly inhibits tumor cell survival and/or proliferation. In NOMO-1 cultures treated with 150 nM or 300 nM MRX-2843, respectively, there are 34.1%±5.6% and 67.1%±2.7% apoptotic and dead cells, compared with 6.8%±0.7% in cultures treated with vehicle (P<0.001). When Kasumi-1 cultures are treated with 50 nM and 100 nM MRX-2843, respectively, colony formation is inhibited by 62.3%±6.4% and 84.1%±7.8% (P<0.01). In NOMO-1 cultures, treatment with 100 nM MRX-2843 inhibits colony formation by 54.8%±18.1% (P<0.001). Treatment with MRX-2843 inhibits downstream signaling via STAT5, ERK1/2, and AKT as well as FLT3 phosphorylation in MOLM-14 cells. Treatment with 50 nM MRX-2843 almost completely inhibits FLT3 activation and its signaling pathways, suggesting that it has a slightly stronger cellular potency against FLT3 than MERTK[1].

ln Vivo

MRX-2843 is 78% orally bioavailable at a dose of 3 mg/kg with a C_max of 1.3 μM and a t_1/2 of 4.4 hours. Quizartinib and MRX-2843 both improve the median survival in MOLM-14 parental xenografts when compared to mice treated with a vehicle (172.5 days versus 40 days and 121 days versus 36 days, respectively, P<0.001). Although higher doses of MRX-2843 are not evaluated, quizartinib is more effective than MRX-2843 in this model (P<0.005). Quizaratinib increases survival in MOLM-14:D835Y xenografts relative to mice treated with a vehicle, although the difference is not statistically significant (median survival 45 days vs. 36 days, P<0.001). MRX-2843 treatment increases survival in MOLM-14:F691L xenografts by nearly two times in both NSG and NSGS mice (median survival 87 vs. 44.5 days and 87 vs. 48 days, respectively, P<0.005). MRX-2843 treatment is associated with improved survival compared to quizartinib treatment; however, this difference is only statistically significant in NSG mice[1].

Cell Assay

Cell lines are cultured (10,000 cells/sample) in 0.35% Noble agar on a 0.5% Noble agar base layer and overlaid with cRPMI containing kinase inhibitor (including MRX-2843) or vehicle. The overlying medium is replaced 2 to 3 times per week, and vehicle treatment is assessed in duplicate. After 14 days or 21 days (Kasumi-1 cells only), colonies are stained with 1 mg/mL nitrotetrazolium blue for 4 hours and counted using a colony counter. Mononuclear cells are isolated from human cord blood and samples from acute myeloid leukemia (AML) patients. Patient samples are cultured in triplicate at a density of 1×10⁶ cells/mL in MethoCult H4434 Classic Methylcellulose-Based Medium with Recombinant Cytokines for Human Cells containing MRX-2843 or vehicle. Colonies are counted after 10 days using the colony counter. Cord blood cells are incubated for 1 hour in serum-free Iscove’s modified Dulbecco’s medium (IMDM) supplemented with BIT 9500 Serum Substitute, low-density lipoproteins, and 2-ME, and then cultured in triplicate at a density of 2×106 cells/mL in Methocult H4434 methylcellulose containing MRX-2843 or vehicle. Colonies are manually counted in a blinded manner after 14 days[1].

References

[1]. The MERTK/FLT3 inhibitor MRX-2843 overcomes resistance-conferring FLT3 mutations in acute myeloid leukemia. JCI Insight. 2016 Mar;1(3):e85630.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C29H40N6O
Molecular Weight	488.6675
Exact Mass	488.33
Elemental Analysis	C, 71.28; H, 8.25; N, 17.20; O, 3.27
CAS #	1429882-07-4
Related CAS #	1429882-07-4;
Appearance	Solid powder
SMILES	CN1CCN(CC1)CC2=CC=C(C=C2)C3=CN(C4=NC(=NC=C34)NCCC5CC5)C6CCC(CC6)O
InChi Key	LBEJYFVJIPQSNX-UHFFFAOYSA-N
InChi Code	InChI=1S/C29H40N6O/c1-33-14-16-34(17-15-33)19-22-4-6-23(7-5-22)27-20-35(24-8-10-25(36)11-9-24)28-26(27)18-31-29(32-28)30-13-12-21-2-3-21/h4-7,18,20-21,24-25,36H,2-3,8-17,19H2,1H3,(H,30,31,32)
Chemical Name	4-[2-(2-cyclopropylethylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol
Synonyms	MRX-2843; UNC 2371; UNC2371A; UNC-2371; UNC-2371A; MRX2843; UNC2371; UNC 2371A; MRX 2843
HS Tariff Code	2934.99.9001
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)

Solubility Data

Solubility (In Vitro)	DMSO: 20~98 mg/mL (200.5 mM) Ethanol: ~25 mg/mL (51.2 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.08 mg/mL (4.26 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 2 mg/mL (4.09 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 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. View More Solubility in Formulation 3: 2 mg/mL (4.09 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 20.0 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. (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: 20~98 mg/mL (200.5 mM)
Ethanol: ~25 mg/mL (51.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.26 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 2: 2 mg/mL (4.09 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 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.

View More

Solubility in Formulation 3: 2 mg/mL (4.09 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 20.0 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.

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

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0464 mL	10.2319 mL	20.4637 mL
	5 mM	0.4093 mL	2.0464 mL	4.0927 mL
	10 mM	0.2046 mL	1.0232 mL	2.0464 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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

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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.

Note： (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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03510104	Active Recruiting	Drug: MRX-2843	Neoplasms Metastatic Cancer	Meryx, Inc.	May 22, 2018	Phase 1
NCT04762199	Recruiting	Drug: Flt3/MerTK Inhibitor MRX-2843 Drug: Osimertinib	Advanced Lung Non-Small Cell Carcinoma Metastatic Lung Non-Small Cell Carcinoma	Emory University	February 24, 2021	Phase 1
NCT04872478	Recruiting	Drug: MRX-2843	Acute Lymphoblastic Leukemia Acute Myeloid Leukemia	Meryx, Inc.	April 1, 2022	Phase 1
NCT04946890	Not yet recruiting	Drug: MRX-2843	Acute Myeloid Leukemia Leukemia	Betta Pharmaceuticals Co., Ltd.	July 1, 2021	Phase 1 Phase 2

Biological Data

MRX-2843 inhibits MERTK activation and downstream signaling and has functional antitumor effects in MERTK+FLT3-WT cell culture and animal models.JCI Insight.2016 Mar;1(3):e85630.
MRX-2843 inhibits FLT3 activation and downstream signaling and has functional antitumor effects in MERTKnegFLT3-ITD cell lines.JCI Insight.2016 Mar;1(3):e85630.
MRX-2843 inhibits colony formation in MERTK-expressing and FLT3-ITD primary AML patient samples.JCI Insight.2016 Mar;1(3):e85630.