HSP990 (NVP-HSP990) 934343-74-5

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

379.39 NVP-HSP990 (HSP990) is a novel, potent and selective HSP90 inhibitor for HSP90α/β with IC50 of 0.6 nM/0.8 nM.


Biological Activity


NVP-HSP990 is based on a
2-amino-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one scaffold,
which is structurally distinct from other known HSP90 Inhibitors.
NVP-HSP990 binds to the N-terminal ATP-binding domain of HSP90.
NVP-HSP990 exhibits single digit nanomolar IC50 values on three of the
HSP90 isoforms (HSP90α, HSP90β, and GRP94) and 320 nM IC50 value on the
fourth (TRAP-1), with selectivity against unrelated enzymes, receptors,
and kinases.


NVP-HSP990 dissociates the HSP90-p23 complex, depleted
client protein c-Met, and induced Hsp70 in c-Met amplified GTL-16
gastric tumor cells. NVP-HSP990 potently inhibites the growth of human
cell lines and primary patient samples from a variety of tumor types.
NVP-HSP990 displays dose- and time-dependent effects on HSP90 client
Proteins. NVP-HSP990 inhibits Glioma tumor-initiating cells (GIC)
proliferation in all GIC lines, with IC50 values ranging approximately
between 10 and 500 nM. Olig2 is a functional marker associated with cell
proliferation and response to NVP-HSP990, as NVP-HSP990 attenuated cell
proliferation in Olig2-high GIC lines. In addition, NVP-HSP990
disrupted cell-cycle control mechanism by decreasing CDK2 and CDK4 and
elevating Apoptosis-related molecules.


NVP-HSP990 exhibits drug-like pharmaceutical and pharmacologic
properties with high oral bioavailability. In the GTL-16 xenograft
model, a single oral administration of 15 mg/kg of NVP-HSP990 induced
sustained downregulation of c-Met and upregulation of Hsp70. In repeat
dosing studies, NVP-HSP990 treatment resulted in tumor growth inhibition
of GTL-16 and Other human tumor xenograft models driven by well-defined
oncogenic HSP90 client proteins.


Protocol(Only for Reference)


Kinase Assay:


[1]

HSP90 binding, ATPase, and selectivity profiling assays	The potency of HSP90 inhibitors for HSP90α, HSP90β, and Grp94 is determined by AlphaScreen competition binding assays, and activity against TRAP-1 is assessed by an ATPase assay.

Cell Assay:


[2]

Cell lines	GICs
Concentrations	~1 μM
Incubation Time	7 days
Method	Dissociated GICs are plated at 10 cells/μL in 6-well plates and incubated with various concentrations of NVP-HSP990 for 7 days. Formed tumorspheres are dissociated into single cells and counted with hemocytometer using 0.2% Trypan blue exclusion.

Animal Study:


[1]

Animal Models	GTL-16, NCI-H1975, BT474, and MV4;11 tumor xenografted nude and SCID mice models
Formulation	100% polyethylene glycol (PEG400)
Dosages	15 mg/kg
Administration	Oral

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Chemical Information

Molecular Weight (MW)	379.39
Formula	C20H18FN5O2
CAS No.	934343-74-5

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms	N/A

Solubility (25°C) *	In vitro	DMSO	75 mg/mL (197.68 mM)
		Water	<1 mg/mL (
		Ethanol	<1 mg/mL (
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	(7R)-2-amino-7-[4-fluoro-2-(6-methoxy-2-pyridinyl)phenyl]-7,8-dihydro-4-methyl-pyrido[4,3-d]pyrimidin-5(6H)-one

Molarity Calculator
Dilution Calculator
Molecular Weight Calculator

Contact us if you need more details on 934343-74-5. We are ready to answer your questions on packaging, logistics, certification or any other aspects about HSP990 934343-74-5、NVP-HSP990 934343-74-5. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Cytoskeletal Signaling > HSP Inhibitor