Mobocertinib mesylate (TAK788 mesylate; AP32788; Exkivity) is an approved drug for the treatment of non-small cell lung cancer (NSCLC) acting as a novel, highly potent, irreversible and orally bioavailable inhibitor of EGFR and HER2 oncogenic mutants (e.g. exon 20 insertions), and exhibits high selectivity over WT EGFR.
Physicochemical Properties
| Molecular Formula | C33H43N7O7S |
| Molecular Weight | 681.802226305008 |
| Exact Mass | 681.294 |
| CAS # | 2389149-85-1 |
| Related CAS # | Mobocertinib;1847461-43-1;Mobocertinib succinate;2389149-74-8 |
| PubChem CID | 146018835 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 48 |
| Complexity | 1030 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | FYPXCXPAJAGDAI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C32H39N7O4.CH4O3S/c1-9-29(40)34-24-16-25(28(42-8)17-27(24)38(6)15-14-37(4)5)35-32-33-18-22(31(41)43-20(2)3)30(36-32)23-19-39(7)26-13-11-10-12-21(23)26;1-5(2,3)4/h9-13,16-20H,1,14-15H2,2-8H3,(H,34,40)(H,33,35,36);1H3,(H,2,3,4) |
| Chemical Name | methanesulfonic acid;propan-2-yl 2-[4-[2-(dimethylamino)ethyl-methylamino]-2-methoxy-5-(prop-2-enoylamino)anilino]-4-(1-methylindol-3-yl)pyrimidine-5-carboxylate |
| 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
| ln Vitro | LU0387 (NPH) cells are inhibited by mobocertinib mesylate (1.5 nM-10 μM; 7 days) with an IC50 of 21 nM [1]. More powerful than WT EGFR (A431 (WT)), mobocertinib mesylate (2 h) effectively suppresses EGFR with common activating mutations (HCC827 (D), HCC4011 (L)), or with the T790M mutation (H1975 (LT)) [1]. In CUTO14 (ASV) cells, mobocertinib mesylate (0.1 nM-1 μM; 6 hours) inhibits pEGFR and pERK1/2 [1]. Impeding EGFR and downstream signaling, mobocertinib mesylate (0.3 nM-1 μM; 6 hours) inhibits [1]. H1781 (HER2 exon 20G776>VC) and Ba/F3 (HER2 exon 20YVMA) cells' HER2 signaling is inhibited by mobocertinib mesylate (0.01, 0.1, and 1 μM; 6 hours) [2]. |
| ln Vivo | Tumor growth is significantly inhibited by mobocertinib mesylate (3, 10, 30 mg/kg; oral; once daily for 20 days) [1]. |
| Cell Assay |
Cell viability assay [1] Cell Types: LU0387 (NPH) Cell Tested Concentrations: 1.5 nM-10 μM Incubation Duration: 7 days Experimental Results: Good inhibitory activity against LU0387 (NPH) cells with an IC50 of 21 nM. Cell viability assay[1] Cell Types: A431 (WT), HCC827 (D), HCC4011 (L), H1975 (LT) Cell Tested Concentrations: Incubation Duration: 2 hrs (hours) Experimental Results: Inhibition of EGFR with common activation of HCC827 (D) mutations, the T790M mutation in HCC4011 (L) cells and H1975 (LT) cells had IC50s of 4, 1.3, and 9.8 nM, respectively, which was more potent than WT EGFR (A431 (WT); IC50 of 35 nM). Western Blot Analysis[1] Cell Types: CUTO14 (ASV) Cell Tested Concentrations: 0.1 nM-1 μM Incubation Duration: 6 hrs (hours) Experimental Results: Strong inhibition of EGFR signaling, reaching 80% inhibition of phosphorylated EGFR (pEGFR) at a concentration of 100 and 100% are nM and 1 μM respectively. Western Blot Analysis[1] Cell Types: HCC827 (D), HCC4011 (L), H1975 (LT) Cell Tested Concentrations: 0.3 nM-1 μM Incubation Duration: 6 hrs (hours) Experimental Results: Potently inhibited EGFR and downstream signaling in HCC827 (D), HCC4011 (L) and H1975 (LT) cells. Western Blot Analysis[2] Cell Types: H1781 (HER2 Exon 20G776>VC), Ba/F3 (HER2 exon 20YVMA) cells Tested Concentrations: 0.01, 0.1 and 1 μM Incubation Duration: 6 h Experimental Results: Inhibited HER2 signaling in H1781 and Ba/F3-HER2 exon 20YVMA mutant cells at 0.1 μM with Dramatically diminished phosphorylations of HER2, AKT, and ERK1/2 in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Animal/Disease Models: Female athymic Nude-Foxn1nu mouse (human NSCLC H1975 LT tumor model) [1]. Doses: 3, 10, 30 mg/kg Route of Administration: Oral; one time/day for 20 days. Experimental Results: Relative to tumor size in the vehicle group, mean tumor volume was diminished by 44% and 92% at 3 mg/kg and 10 mg/kg, respectively. 30 mg/kg induced 76% tumor regression relative to pre-treatment tumor size. |
| References |
[1]. Gonzalvez F, et al. Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non-Small Cell Lung Cancer. Cancer Discov. 2021 Jul;11(7):1672-1687. [2]. Han H, et al. Targeting HER2 Exon 20 Insertion-Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib. Cancer Res. 2021 Oct 15;81(20):5311-5324. |
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 | 1.4667 mL | 7.3335 mL | 14.6671 mL | |
| 5 mM | 0.2933 mL | 1.4667 mL | 2.9334 mL | |
| 10 mM | 0.1467 mL | 0.7334 mL | 1.4667 mL |