CB-5083p97 inhibitor CAS# 1542705-92-9 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1542705-92-9 | SDF | Download SDF |
| PubChem ID | 73051434 | Appearance | Powder |
| Formula | C24H23N5O2 | M.Wt | 413.47 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (241.86 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 1-[4-(benzylamino)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl]-2-methylindole-4-carboxamide | ||
| SMILES | CC1=CC2=C(C=CC=C2N1C3=NC4=C(COCC4)C(=N3)NCC5=CC=CC=C5)C(=O)N | ||
| Standard InChIKey | RDALZZCKQFLGJP-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C24H23N5O2/c1-15-12-18-17(22(25)30)8-5-9-21(18)29(15)24-27-20-10-11-31-14-19(20)23(28-24)26-13-16-6-3-2-4-7-16/h2-9,12H,10-11,13-14H2,1H3,(H2,25,30)(H,26,27,28) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | CB-5083 is a potent, selective and orally bioavailable p97 inhibitor with an IC50 value of 11 nM.In Vitro:Treatment of tumor cells with CB-5083 leads to significant accumulation of markers associated with inhibition of ubiquitin−proteasome system and endoplasmic reticulum-associated degradation functions, which induces irresolvable proteotoxic stress and cell death[1]In Vivo:In tumor bearing mice, oral administration of CB-5083 causes rapid accumulation of markers of the unfolded protein response and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. CB-5083 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors[1]. References: | |||||
CB-5083 Dilution Calculator
CB-5083 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4186 mL | 12.0928 mL | 24.1856 mL | 48.3711 mL | 60.4639 mL |
| 5 mM | 0.4837 mL | 2.4186 mL | 4.8371 mL | 9.6742 mL | 12.0928 mL |
| 10 mM | 0.2419 mL | 1.2093 mL | 2.4186 mL | 4.8371 mL | 6.0464 mL |
| 50 mM | 0.0484 mL | 0.2419 mL | 0.4837 mL | 0.9674 mL | 1.2093 mL |
| 100 mM | 0.0242 mL | 0.1209 mL | 0.2419 mL | 0.4837 mL | 0.6046 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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IC50: 15.4 nM
CB-5083 is an orally bioavailable inhibitor of p97. P97 is an AAA-ATPase involved in multiple cellular functions such as organelle membrane homotypic fusion and sorting of endosomal cargo. P97 is also known as valosin-containing protein which plays important roles in regulating protein homeostasis [1].
In vitro: CB-5083 is a selective potent inhibitor of p97’s second ATPase domain. CB-5083 might compete with ATP for the same binding site but may adopt a different orientation [2]. The IC50 of CB-5083 against wild-type (WT) p97 was 15.4?nM. CB-5083 could dose-dependently increase the cytosolic protein degradation in HEK293T, A549 and HCT116 cell lines [1]. CB-5083 treatment (2.5 μM) of A549 cells for 24h could induce cancer cell death [1].
In vivo: In female nude mice bearing HCT116, A549 lung carcinoma, and AMO-1 multiple myeloma xenograft tumors, oral administration of CB-5083 (100?mg/kg) for 6 h showed a significant antitumor response in tumors (TGI?= 63%, p?< 0.0001) [1,2].
Clinical trial: CB-5083 has entered phase 1 clinical trials in patients with multiple myeloma and solid tumors.
References:
Anderson D J, Le Moigne R, Djakovic S, et al. Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis[J]. Cancer cell, 2015, 28(5): 653-665.
Zhou H J, Wang J, Yao B, et al. Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)[J]. Journal of medicinal chemistry, 2015, 58(24): 9480-9497.
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Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083).[Pubmed:26565666]
J Med Chem. 2015 Dec 24;58(24):9480-97.
The AAA-ATPase p97 plays vital roles in mechanisms of protein homeostasis, including ubiquitin-proteasome system (UPS) mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and autophagy. Herein we describe our lead optimization efforts focused on in vitro potency, ADME, and pharmaceutical properties that led to the discovery of a potent, ATP-competitive, D2-selective, and orally bioavailable p97 inhibitor 71, CB-5083. Treatment of tumor cells with 71 leads to significant accumulation of markers associated with inhibition of UPS and ERAD functions, which induces irresolvable proteotoxic stress and cell death. In tumor bearing mice, oral administration of 71 causes rapid accumulation of markers of the unfolded protein response (UPR) and subsequently induces apoptosis leading to sustained antitumor activity in in vivo xenograft models of both solid and hematological tumors. 71 has been taken into phase 1 clinical trials in patients with multiple myeloma and solid tumors.
