Physicochemical Properties
| Molecular Formula | C42H51N9O5 |
| Molecular Weight | 761.91 |
| Exact Mass | 761.401 |
| CAS # | 2485861-07-0 |
| PubChem CID | 139416847 |
| Appearance | White to off-white solid powder |
| LogP | 2.7 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 56 |
| Complexity | 1560 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O1CCC(CC1)N1CCN(C2C=CC(=CC=2NC(C=C)=O)NC2C(N(C)C=C(C3C=CN=C(C=3CO)N3C(C4=CC5=C(CC(C)(C)C5)N4CC3)=O)N=2)=O)[C@@H](C)C1 |
| InChi Key | OYJVFTNYBWVQHA-SANMLTNESA-N |
| InChi Code | InChI=1S/C42H51N9O5/c1-6-37(53)45-32-20-28(7-8-34(32)49-14-13-48(23-26(49)2)29-10-17-56-18-11-29)44-38-41(55)47(5)24-33(46-38)30-9-12-43-39(31(30)25-52)51-16-15-50-35(40(51)54)19-27-21-42(3,4)22-36(27)50/h6-9,12,19-20,24,26,29,52H,1,10-11,13-18,21-23,25H2,2-5H3,(H,44,46)(H,45,53)/t26-/m0/s1 |
| Chemical Name | N-[5-[[6-[2-(4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl)-3-(hydroxymethyl)pyridin-4-yl]-4-methyl-3-oxopyrazin-2-yl]amino]-2-[(2S)-2-methyl-4-(oxan-4-yl)piperazin-1-yl]phenyl]prop-2-enamide |
| 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
| References |
[1]. Preparation of pyrrolopyrazines and related heterocycles as inhibitors of BTK and mutants thereof for the treatment of neoplastic, autoimmune and inflammatory disorders. World Intellectual Property Organization, WO2020176403 A1 2020-09-03. |
| Additional Infomation | Rocbrutinib is an orally bioavailable inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon oral administration, rocbrutinib covalently binds to and inhibits the activity of wild-type (WT) BTK and non-covalently binds to inhibits the activity of C481 mutated BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481 (C481S). This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes. BTK C481S mutation plays an important role in resistance to certain BTK inhibitors. This dual activity allows efficacy against tumor cells expressing WT BTK through covalent binding while simultaneously preventing the proliferation of tumor cells expressing the most common resistance mutation to covalent BTK inhibitors through non-covalent binding. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3125 mL | 6.5625 mL | 13.1249 mL | |
| 5 mM | 0.2625 mL | 1.3125 mL | 2.6250 mL | |
| 10 mM | 0.1312 mL | 0.6562 mL | 1.3125 mL |