CRK12-IN-1 is a potent inhibitor of CRK12. CRK12-IN-1 has strong resistance to Trypanosoma brucei (Tb brucei) and can quickly kill pathogenic cells. It is also effective against T. congolense (EC50 is 1.3 and 18 nM respectively).

Physicochemical Properties

Molecular Formula	C20H26F2N4O3S2
Molecular Weight	472.572248935699
Exact Mass	472.141
CAS #	1990479-14-5
PubChem CID	122479916
Appearance	Typically exists as solid at room temperature
LogP	5.1
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	31
Complexity	704
Defined Atom Stereocenter Count	0
InChi Key	DZBBFJPWMFEESI-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H26F2N4O3S2/c1-11(2)10-31(28,29)26-13-8-6-12(7-9-13)24-20-25-19(23)18(30-20)17(27)16-14(21)4-3-5-15(16)22/h3-5,11-13,26H,6-10,23H2,1-2H3,(H,24,25)
Chemical Name	N-[4-[[4-amino-5-(2,6-difluorobenzoyl)-1,3-thiazol-2-yl]amino]cyclohexyl]-2-methylpropane-1-sulfonamide
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	CRK12-IN-1 (Compound 1) (10 mg/mL; 69 hours) is a powerful inhibitor of tuberculosis in the Congo (EC50 of 18 nM and 1.3 nM, respectively), and it is also very efficient against tuberculosis and animal models of tuberculosis infection[1].
ln Vivo	CRK12-IN-1 (compound 1) (50 or 10 mg/kg; subcutaneous injection; once daily for 4 days) promotes sterile cure of Trypanosoma congolense-infected mice and has the same effect but is somewhat more effective. Effective (30 or 3 mg/kg; subcutaneous injection; daily for 4 days) against Plasmodium vivax -infected mice [1]. CRK12-IN-1 (5 mg/kg, subcutaneous injection, twice 12 hours each for 4 days) lowers parasitemia below detectable levels in Trypanosoma congolense-infected calves, but not after therapy is withdrawn Parasitaemia promptly recovers [1] . CRK12-IN-1 (10 mg free base/kg; subcutaneous injection; 0.08-8 hours) shows 74% bioavailability in female NMRI mice with a half-life of approximately 1 hour [1]. CRK12-IN-1 (5 mg free base/kg IM or 2.5 mg free base/kg IV; 0.25-120 hours) has moderate blood clearance and a relatively short half-life (about 1.8 hours). Male ruminant Holstein-Friesian cattle and penetrate tissues beyond the vasculature [1].
References	[1]. Smith A, et al. Repositioning of a Diaminothiazole Series Confirmed to Target the Cyclin-Dependent Kinase CRK12 for Use in the Treatment of African Animal Trypanosomiasis [published online ahead of print, 2022 Mar 18]. J Med Chem. 2022;10.1021/acs.jmedche

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1161 mL	10.5804 mL	21.1609 mL
	5 mM	0.4232 mL	2.1161 mL	4.2322 mL
	10 mM	0.2116 mL	1.0580 mL	2.1161 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.