This product has been discontinued from InvivoChem. PU-H71 (also known as NSC-750424; PU-H-71) is a novel, highly potent and selective inhibitor of HSP90 with anticancer activity. It inhibits HSP90 with IC50 of 51 nM. PU-H71 showed anti-tumor effects in TNBC xenografts, including complete response and tumor regression, without toxicity to the host are achieved with this agent. PU-H71 induces efficient and sustained downregulation and inactivation, both in vitro and in vivo, of these proteins.

Physicochemical Properties

Molecular Formula	C18H21IN6O2S
Molecular Weight	512.37
Exact Mass	512.049
CAS #	873436-91-0
Related CAS #	Zelavespib hydrochloride
PubChem CID	9549213
Appearance	White to off-white solid powder
Density	1.8±0.1 g/cm3
Boiling Point	650.6±65.0 °C at 760 mmHg
Flash Point	347.3±34.3 °C
Vapour Pressure	0.0±1.9 mmHg at 25°C
Index of Refraction	1.777
LogP	4.11
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	7
Heavy Atom Count	28
Complexity	521
Defined Atom Stereocenter Count	0
InChi Key	SUPVGFZUWFMATN-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H21IN6O2S/c1-10(2)21-4-3-5-25-17-15(16(20)22-8-23-17)24-18(25)28-14-7-13-12(6-11(14)19)26-9-27-13/h6-8,10,21H,3-5,9H2,1-2H3,(H2,20,22,23)
Chemical Name	8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine
Synonyms	PU-H71; PU H71; PU-H 71;NSC 750424; NSC-750424.
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	Zelavespib is a strong Hsp90 product with an IC50 of 51 nM in MDA-MB-468 cells. Zelavespib inhibits the growth of multiple tumor cells, such as MDA-MB-468, MDA-MB-231, and HCC-1806 cells, with IC50s of 65 ± 8 nM, 140 ± 5 nM, and 87 ± 3 nM, respectively. This inhibition is consistent with G2-M blockade associated. Zelavespib (10-1000 nM) can significantly induce triple-negative breast cancer (TNBC). Zelavespib (0.5, 1 μM) can also induce potential cancer proteins in TNBC [1]. Zelavespib (0.5 μM) reduces and senescence BCR signaling disruption. Zelavespib (0.25-10 μM) is cytotoxic to CLL cells. Additionally, Zelavespib (0-1μM) reduces CLL viability by inducing mitochondria and antagonizes survival signals from the CLL microenvironment at 0.5 μM [2]. Zelavespib (0.05 μM) induces MDA-MB-231, BT-474, and MCF7 cells, and TNF-α enhances this induction. Zelavespib (0.05 μM) promotes IKKβ and activates NF-κB activity induced by TNF-α processing [3].
ln Vivo	In MDA-MB-468 tumor-bearing mice, zelavespib (75 mg/kg, i.p.) resulted in intratumoral accumulation, extended downregulation of antitumor driving molecules, and completed and retained responses at nontoxic levels. Zelavespib (75 mg/kg, intraperitoneally, for 3 weeks) slows the growth of tumors; this action is linked to the downregulation of several malignant kinesins regulated by Hsp90 [1].
Animal Protocol	Dissolved in PBS; 75 mg/kg; i.p. injection Human triple-negative breast cancers xenografts MDA-MB-231
References	[1]. Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8368-73. [2]. HSP90 stabilizes B-cell receptor kinases in a multi-client interactome: PU-H71 induces CLL apoptosis in a cytoprotective microenvironment. Oncogene. 2017 Jun 15;36(24):3441-3449. [3]. PU-H71 effectively induces degradation of IκB kinase β in the presence of TNF-α. Mol Cell Biochem. 2014 Jan;386(1-2):135-42.
Additional Infomation	Zelavespib (PU-H71) has been used in trials studying the treatment of LYMPHOMA, Solid Tumors, Metastatic Solid Tumor, and Myeloproliferative Neoplasms (MPN). Zelavespib is a purine-based heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Zelavespib specifically inhibits active Hsp90, thereby inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. This may result in the inhibition of cellular proliferation in susceptible tumor cell populations. Hsp90, a molecular chaperone protein, is upregulated in a variety of tumor cell types.

Solubility Data

Solubility (In Vitro)

DMSO: 100 mg/mL (195.2 mM) Water:<1 mg/mL Ethanol:100 mg/mL (195.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 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 25.0 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: ≥ 2.5 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.88 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 25.0 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	1.9517 mL	9.7586 mL	19.5171 mL
	5 mM	0.3903 mL	1.9517 mL	3.9034 mL
	10 mM	0.1952 mL	0.9759 mL	1.9517 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.