MIK665 (also known as MIK-665; S-64315) is a novel, investigational and specific Mcl-1 inhibitor with an IC50 of 1.81 nM. Potential pro-apoptotic and anti-cancer properties of MIK665. It binds to and prevents the activity of Mcl-1, which causes cells that overexpress Mcl-1 to proliferate. The Bcl-2 family of proteins member Mcl-1, an anti-apoptotic protein, is upregulated in cancer cells and supports the survival of tumor cells. MCL-1, a protein belonging to the BCL-2 family that inhibits apoptosis, is a crucial regulator of mitochondrial homeostasis. MCL-1 is an alluring target for cancer therapy due to its frequent overexpression in human primary cancer cells and drug-resistant cancer cells. Three MCL-1 selective inhibitors have made it to clinical trials as a result of significant advancements in the development of small-molecule MCL-1 inhibitors in recent years.

Physicochemical Properties

Molecular Formula	C47H44CLFN6O6S
Molecular Weight	875.41
Exact Mass	874.27
Elemental Analysis	C, 64.49; H, 5.07; Cl, 4.05; F, 2.17; N, 9.60; O, 10.97; S, 3.66
CAS #	1799631-75-6
Related CAS #	(R)-MIK665;1799831-02-9
PubChem CID	118157243
Appearance	White to off-white solid powder
LogP	6.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	14
Rotatable Bond Count	16
Heavy Atom Count	62
Complexity	1390
Defined Atom Stereocenter Count	1
SMILES	CC1=C(C=CC(=C1Cl)OCCN2CCN(CC2)C)C3=C(SC4=NC=NC(=C34)O[C@H](CC5=CC=CC=C5OCC6=NC(=NC=C6)C7=CC=CC=C7OC)C(=O)O)C8=CC=C(C=C8)F
InChi Key	PKYIMGFMRFVOMB-LDLOPFEMSA-N
InChi Code	InChI=1S/C47H44ClFN6O6S/c1-29-34(16-17-38(42(29)48)59-25-24-55-22-20-54(2)21-23-55)40-41-45(51-28-52-46(41)62-43(40)30-12-14-32(49)15-13-30)61-39(47(56)57)26-31-8-4-6-10-36(31)60-27-33-18-19-50-44(53-33)35-9-5-7-11-37(35)58-3/h4-19,28,39H,20-27H2,1-3H3,(H,56,57)/t39-/m1/s1
Chemical Name	(2R)-2-[5-[3-chloro-2-methyl-4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]-6-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxy-3-[2-[[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl]propanoic acid
Synonyms	S 64315; MIK-665; S-64315; MIK665; S64315; MIK 665
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

Targets	Mcl-1 (IC50 = 1.81 nM)
ln Vitro	When paired with ABT-199, MIK665 (S-64315) has synergistic effects akin to those of S63845. Comparable results have been observed in terms of reducing cell viability in typical melanoma cell lines (MB2141, MB3616, MB3961, MB4667, A375, and 1205Lu cells) when S64315 (0.156-10 μM) and ABT-199 (625 nM) are combined. The chemical preparation 13 of patent WO2016207225A1, which contains MIK665, inhibits H929 cells with an IC50 of 250 nM [2].
References	[1]. Simultaneously Inhibiting BCL2 and MCL1 Is a Therapeutic Option for Patients with Advanced Melanoma. Cancers (Basel). 2020;12(8):2182. Published 2020 Aug 5. [2]. New hydroxyester derivatives, a process for their preparation and pharmaceutical compositions containing them. WO2016207225A1.

Solubility Data

Solubility (In Vitro)

DMSO: ≥125 mg/mL (~142.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (2.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (2.38 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 3: 5%DMSO+40%PEG300+5%Tween80+50%ddH2O: 5 mg/ml  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.1423 mL	5.7116 mL	11.4232 mL
	5 mM	0.2285 mL	1.1423 mL	2.2846 mL
	10 mM	0.1142 mL	0.5712 mL	1.1423 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.