AZ82 is a selective inhibitor of the kinesin-like protein KIFC1 (HSET/KIFC1) with Ki and IC50s of 43 nM and 300 nM, respectively.

Physicochemical Properties

Molecular Formula	C28H31F3N4O3S
Molecular Weight	560.630955934525
Exact Mass	560.206
CAS #	1449578-65-7
PubChem CID	91885438
Appearance	White to off-white solid powder
LogP	5.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	10
Heavy Atom Count	39
Complexity	819
Defined Atom Stereocenter Count	2
SMILES	S1C(C)=C(CCC)C=C1C(N[C@H](CC1C=NC(C2C=CC=C(C=2)OC(F)(F)F)=CC=1)C(N[C@H]1CNCC1)=O)=O
InChi Key	PMTLKNOARSHUJB-ZJSXRUAMSA-N
InChi Code	InChI=1S/C28H31F3N4O3S/c1-3-5-19-14-25(39-17(19)2)27(37)35-24(26(36)34-21-10-11-32-16-21)12-18-8-9-23(33-15-18)20-6-4-7-22(13-20)38-28(29,30)31/h4,6-9,13-15,21,24,32H,3,5,10-12,16H2,1-2H3,(H,34,36)(H,35,37)/t21-,24-/m1/s1
Chemical Name	5-methyl-N-[(2R)-1-oxo-1-[[(3R)-pyrrolidin-3-yl]amino]-3-[6-[3-(trifluoromethoxy)phenyl]pyridin-3-yl]propan-2-yl]-4-propylthiophene-2-carboxamide
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

AZ82 lightning-induced multipolar spindles in BT-549 cells, but not in IR with normal centrosome counts, such as HeLa [1]. AZ82 binds to the KIFC1/MT complex but not to KIFC1 or MT alone. Treatment with AZ82 resulted in centrosome declustering and centrosome amplification in BT-549 breast cancer cells. The IC50 of AZ82 that inhibits mant-ATP binding is 0.90 ± 0.09 μM, whereas the IC50 that releases mant-ADP is 1.26 ± 0.51μM[2].

References

[1]. Causes and consequences of centrosome abnormalities in cancer. Philos Trans R Soc Lond B Biol Sci. 2014 Sep 5;369(1650). [2]. ACS Chem Biol. 2013 Oct 18;8(10):2201-8.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~222.96 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.71 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 (3.71 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7837 mL	8.9185 mL	17.8371 mL
	5 mM	0.3567 mL	1.7837 mL	3.5674 mL
	10 mM	0.1784 mL	0.8919 mL	1.7837 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.