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| 25mg |
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Purity: ≥98%
NVP-HSP990 (NVP HSP 990; NVP-HSP-990; HSP990; HSP-990) is an orally bioavailable HSP90 (heat shock protein 90) inhibitor with potential antitumor activity. It inhibits HSP90α/β with IC50s of 0.6 nM/0.8 nM. NVP-HSP990 exhibits low nanomolar (single digit IC50 values) activity against various Hsp90 isoforms (Hsp90α, Hsp90β, and GRP94) and high selectivity over unrelated enzymes, receptors, and kinases.
| ln Vitro |
Strong and specific against Hsp90, NVP-HSP990 has IC50 values of 0.6, 0.8, and 8.5 nM for Hsp90α, Hsp90β, and Grp94, in that order. Topoisomerase II, a GHKL (Gyrase, Hsp90, Histidine Kinase, MutL) family ATPase that is closely related to Hsp90, exhibits no change in ATPase activity when exposed to 10 μM of NVP-HSP990. In CTL-16 cells, NVP-HSP990 also effectively affects c-Met, Hsp70, p-ERK, and p-AKT, with EC50 values of 37 ± 4, 20 ± 2, 11 ± 1, and 6 ± 1 nM, in that order. BT474, A549, H1975, and MV4;11 cells are inhibited from proliferating by NVP-HSP990, with GI50 values of 7 ± 2, 28 ± 5, 35 ± 4, and 4 ± 1 nM, respectively[1]. With an EC50 of 14 nM, NVP-HSP990 suppresses the cellular growth of GTL-16[2]. Multiple myeloma cell lines are inhibited by NVP-HSP990 (5-500 nM), with IC50s of 27-49 nM following a 72-hour treatment period. NVP-HSP990 causes cell cycle arrest in the G2/M phase (25-200 nM), produces apoptosis via caspase-8 followed by caspase-3 activation (100 nM), and causes apoptosis in multiple myeloma cell lines (0-100 nM). NVP-HSP990 interacts with Akt and ERK signaling and upregulates HSP70 expression. Additionally, NVP-HSP990 (100 nM) and melphalan together have synergistic effects on multiple myeloma cell growth inhibition. They also boost caspase-3, caspase-8, and caspase-9 cleavage and activate caspase-2[3]. NVP-
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| ln Vivo |
In GTL-16 tumor-bearing mice, NVP-HSP990 (2.5 to 5 mg/kg twice weekly, or 5 to 15 mg/kg weekly, po) causes dose-proportionate anticancer effectiveness, without evident loss or overt indications of toxicity. In the BT-474 breast cancer model, NVP-HSP990 (5 or 10 mg/kg weekly, po) likewise significantly inhibits the growth of tumors. In the MV4;11 xenograft model, NVP-HSP990 (5 mg/kg twice weekly or 15 mg/kg weekly, po) slows the growth of the tumor. Additionally, in H1975 and A549 tumor models, NVP-HSP990 (0.5 mg/kg daily, 14, 5 mg/kg twice weekly, or 15 mg/kg weekly, po) exhibits antitumor efficaciousness[1]. NVP-HSP990 (5, 15 mg/kg, po) demonstrates anticancer activity in a GTL-16 tumor xenograft and a prolonged suppression of c-Met levels with a 30% and 50% reduction[2].
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| References |
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| Molecular Formula |
C20H18FN5O2
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| Molecular Weight |
379.39
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| Exact Mass |
379.144
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| CAS # |
934343-74-5
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| Related CAS # |
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| PubChem CID |
46216556
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.627
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| LogP |
1.44
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
567
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C2C(=NC(=N1)N)C[C@@H](NC2=O)C3=C(C=C(C=C3)F)C4=NC(=CC=C4)OC
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| InChi Key |
WSMQUUGTQYPVPD-OAHLLOKOSA-N
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| InChi Code |
InChI=1S/C20H18FN5O2/c1-10-18-16(26-20(22)23-10)9-15(25-19(18)27)12-7-6-11(21)8-13(12)14-4-3-5-17(24-14)28-2/h3-8,15H,9H2,1-2H3,(H,25,27)(H2,22,23,26)/t15-/m1/s1
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| Chemical Name |
(7R)-2-amino-7-[4-fluoro-2-(6-methoxypyridin-2-yl)phenyl]-4-methyl-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.48 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 (5.48 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 | 2.6358 mL | 13.1791 mL | 26.3581 mL | |
| 5 mM | 0.5272 mL | 2.6358 mL | 5.2716 mL | |
| 10 mM | 0.2636 mL | 1.3179 mL | 2.6358 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01064089 | Terminated | Drug: HSP990 | Advanced Solid Tumors | Novartis Pharmaceuticals | February 2010 | Phase 1 |
| NCT00879905 | Completed | Drug: HSP990 | Advanced Solid Malignancies | Novartis Pharmaceuticals | May 2009 | Phase 1 |
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