Synonym
RBC8; RBC-8; RBC 8.
IUPAC/Chemical Name
6-Amino-4-(2,5-dimethoxyphenyl)-1,4-dihydro-3-(2-naphthalenyl)pyrano[2,3-c]pyrazole-5-carbonitrile
InChi Key
CLMQBVUFKIKYLU-UHFFFAOYSA-N
InChi Code
InChI=1S/C25H20N4O3/c1-30-17-9-10-20(31-2)18(12-17)21-19(13-26)24(27)32-25-22(21)23(28-29-25)16-8-7-14-5-3-4-6-15(14)11-16/h3-12,21H,27H2,1-2H3,(H,28,29)
SMILES Code
N#CC(C1C2=CC(OC)=CC=C2OC)=C(N)OC3=C1C(C4=CC=C5C=CC=CC5=C4)=NN3
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, DMF, and ethanol
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO, DMF, and ethanol
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
RBC8 prevents binding of the GTPase to the Ral-binding protein. RBC8 prevented Ral-mediated spreading of murine embryonic fibroblasts, blocked anchorage-independent growth of H2122 and H358 lung cancer cell lines (IC50s = 3.5 and 3.4 µM, respectively), and inhibited the growth of H2122 lung cancer xenografts in mice (50 mg/kg i.p.).
In vitro activity:
To be determined
In vivo activity:
RBC8 and BQU57 show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference.
Reference: Nature. 2014 Nov 20;515(7527):443-7. https://pubmed.ncbi.nlm.nih.gov/25219851/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
30.0 |
70.68 |
| DMSO |
30.0 |
70.68 |
| Ethanol |
0.3 |
0.59 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
424.46
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Walsh TG, Wersäll A, Poole AW. Characterisation of the Ral GTPase inhibitor RBC8 in human and mouse platelets. Cell Signal. 2019 Jul;59:34-40. doi: 10.1016/j.cellsig.2019.03.015. Epub 2019 Mar 14. PMID: 30880223; PMCID: PMC6510928.
2. Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, Meier J, Hoffman B, Owens C, Wysoczynski CL, Nitz MD, Knabe WE, Ahmed M, Brautigan DL, Paschal BM, Schwartz MA, Jones DN, Ross D, Meroueh SO, Theodorescu D. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov 20;515(7527):443-7. doi: 10.1038/nature13713. Epub 2014 Sep 14. PMID: 25219851; PMCID: PMC4351747.
In vitro protocol:
To be determined
In vivo protocol:
1. Walsh TG, Wersäll A, Poole AW. Characterisation of the Ral GTPase inhibitor RBC8 in human and mouse platelets. Cell Signal. 2019 Jul;59:34-40. doi: 10.1016/j.cellsig.2019.03.015. Epub 2019 Mar 14. PMID: 30880223; PMCID: PMC6510928.
2. Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, Meier J, Hoffman B, Owens C, Wysoczynski CL, Nitz MD, Knabe WE, Ahmed M, Brautigan DL, Paschal BM, Schwartz MA, Jones DN, Ross D, Meroueh SO, Theodorescu D. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov 20;515(7527):443-7. doi: 10.1038/nature13713. Epub 2014 Sep 14. PMID: 25219851; PMCID: PMC4351747.
1: Walsh TG, Wersäll A, Poole AW. Characterisation of the Ral GTPase inhibitor RBC8 in human and mouse platelets. Cell Signal. 2019 Jul;59:34-40. doi: 10.1016/j.cellsig.2019.03.015. Epub 2019 Mar 14. PMID: 30880223; PMCID: PMC6510928.
2: Kodama T, Bard-Chapeau EA, Newberg JY, Kodama M, Rangel R, Yoshihara K, Ward JM, Jenkins NA, Copeland NG. Two-step Forward Genetic Screen in Mice Identifies Ral GTPase-activating Proteins as Suppressors of Hepatocellular Carcinoma. Gastroenterology. 2016 May 10. pii: S0016-5085(16)34392-X. doi: 10.1053/j.gastro.2016.04.040. [Epub ahead of print] PubMed PMID: 27178121.
3: Gu C, Feng M, Yin Z, Luo X, Yang J, Li Y, Li T, Wang R, Fei J. RalA, a GTPase targeted by miR‑181a, promotes transformation and progression by activating the Ras‑related signaling pathway in chronic myelogenous leukemia. Oncotarget. 2016 Mar 8. doi: 10.18632/oncotarget.7987. [Epub ahead of print] PubMed PMID: 26967392.
4: Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, Meier J, Hoffman B, Owens C, Wysoczynski CL, Nitz MD, Knabe WE, Ahmed M, Brautigan DL, Paschal BM, Schwartz MA, Jones DN, Ross D, Meroueh SO, Theodorescu D. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov 20;515(7527):443-7. doi: 10.1038/nature13713. Epub 2014 Sep 14. PubMed PMID: 25219851; PubMed Central PMCID: PMC4351747.
