KU-177 is a potent inhibitor of Hsp90 ATPase homolog 1 (Aha1) and ablate Aha1-driven enhancement of Hsp90-dependent tau aggregation. KU-177 also interferes with the Aha1/Hsp90 interaction (IC50=4.08 μM) but does not affect the ability of Hsp90 to refold luciferase. KU-177 suppresses the growth of cancer/tumor cells and causes apoptosis, and may be utilized in the research/study of Tau disease.

Physicochemical Properties

Molecular Formula	C27H23NO8
Molecular Weight	489.473428010941
Exact Mass	489.142
CAS #	1160952-43-1
PubChem CID	53261526
Appearance	Typically exists as solid at room temperature
LogP	4.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	8
Heavy Atom Count	36
Complexity	844
Defined Atom Stereocenter Count	0
InChi Key	DKZHANZAVOELPJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H23NO8/c1-15(29)35-23-11-8-17-14-21(27(31)36-24(17)25(23)34-4)28-26(30)18-9-10-22(33-3)20(13-18)16-6-5-7-19(12-16)32-2/h5-14H,1-4H3,(H,28,30)
Chemical Name	[8-methoxy-3-[[4-methoxy-3-(3-methoxyphenyl)benzoyl]amino]-2-oxochromen-7-yl] acetate
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	KU-177 (50 μM; 48 hours) prevents initial multiple myeloma (MM) and relapsed MM patient samples' MRD-positive cells from proliferating by flow cytometry [1]. Protease activity in AHSA1 WT/OE, PSMD2 WT/OE, and ANBL6 WT/DR cells is inhibited by KU-177 (30 μM; 48 hours) [1]. Increased AHSA1-induced cell proliferation and PI resistance are eliminated by KU-177, which also lowers CDK6 and PSMD2 expression [1]. KU-177 (25 μM; 30 min; 37℃) prevents recombinant P301L tau protein from aggregating, but it has no effect on Hsp90 refolding luciferase [2]. In SH-SY5Y neuroblastoma cells and SK-BR-3 breast cancer cells, KU-177 (10 μM; 24 hours) inhibits Aha1 and Hsp90 interaction, but not the Hsp90 client protein (Her2) inhibitory effect[2].
ln Vivo	KU-177 (1 mg/kg; i.p.; twice weekly; 4 weeks) inhibits tumor growth and extends survival of 5TMM3VT MM mice without apparent toxicity. KU-177 showed enhanced in vivo efficacy when combined with bortezomib (1 mg/kg; i.p.) [1].
Cell Assay	Cell proliferation assay[1] Cell Types: ARP1 and H929 WT and AHSA1-OE Cell Tested Concentrations: 1 nM-100 μM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: AHSA1-induced multiple myeloma (MM) cell proliferation and PI Resistance reduction/HSP90 in vitro. Cell proliferation assay [2] Cell Types: SH-SY5Y neuroblastoma cells and Her2 overexpressing SK-BR-3 breast cancer cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: No degradation of Hsp90 client protein Her2 is induced (in (in SK-BR-3 cells), Cdk6 or pAktS473 (in SHSY5Y cells), nor did it induce the expression of Hsp70 (a heat shock response marker).
Animal Protocol	Animal/Disease Models: 5TMM3VT mouse model (6-8 weeks old, C57BL/KaLwrij mice) [1] Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; twice a week; mice with hindlimb weakness were sacrificed immediately, approx. Results at 4-5 weeks: Inhibition of xenograft tumor growth of ANBL6 WT/BTZ-DR cells. It did not cause histopathological abnormalities or lesions in major organs such as the heart, liver, spleen, lungs, and kidneys.
References	[1]. AHSA1 is a promising therapeutic target for cellular proliferation and proteasome inhibitor resistance in multiple myeloma. J Exp Clin Cancer Res. 2022 Jan 6;41(1):11. [2]. Synthesis and Evaluation of Small Molecule Disruptors of the Aha1/Hsp90 Complex for the Reduction of Tau Aggregation. ACS Med Chem Lett. 2022 Apr 15;13(5):827-832.

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	2.0430 mL	10.2151 mL	20.4303 mL
	5 mM	0.4086 mL	2.0430 mL	4.0861 mL
	10 mM	0.2043 mL	1.0215 mL	2.0430 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.