Gamcemetinib (CC-99677) is a potent, covalent, irreversible inhibitor of the mitogen-activated protein (MAP) kinase-activated protein kinase-2 (MK2) pathway on a biochemical (IC50=156.3 nM) and cellular basis It has an effect in detection (EC50=89 nM). Gamcemetinib is from patent WO2020236636, compound 1.

Physicochemical Properties

Molecular Formula	C22H20CLN5O3S
Molecular Weight	469.94
Exact Mass	469.097
CAS #	1887069-10-4
Related CAS #	1887069-10-4;
PubChem CID	118936948
Appearance	Light yellow to yellow solid powder
LogP	4.5
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	678
Defined Atom Stereocenter Count	1
SMILES	N1[C@@H](CNC2C3=C(C=CC4=NC(OC5C(COCC)=CN=C(Cl)N=5)=CC=C34)SC=2C1=O)C
InChi Key	PYOQIOLRFIRRSO-LLVKDONJSA-N
InChi Code	InChI=1S/C22H20ClN5O3S/c1-3-30-10-12-9-25-22(23)28-21(12)31-16-7-4-13-14(27-16)5-6-15-17(13)18-19(32-15)20(29)26-11(2)8-24-18/h4-7,9,11,24H,3,8,10H2,1-2H3,(H,26,29)/t11-/m1/s1
Chemical Name	(15R)-5-[2-chloro-5-(ethoxymethyl)pyrimidin-4-yl]oxy-15-methyl-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one
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)

Biological Activity

ln Vitro	In biochemical (IC50=156.3 nM) and cell-based studies (EC50 = 89 nM), gamcemetinib is a strong, covalent, irreversible activator of mitogen-activated protein (MAP)-activated mitogen-activated protein-2 (MK2)[1].
References	[1]. WO2020236636.

Solubility Data

Solubility (In Vitro)

DMSO : ~37.5 mg/mL (~79.80 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 1.5 mg/mL (3.19 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 + to the above solution and mix evenly; then add 450 μL of 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1279 mL	10.6397 mL	21.2793 mL
	5 mM	0.4256 mL	2.1279 mL	4.2559 mL
	10 mM	0.2128 mL	1.0640 mL	2.1279 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.