| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
|
| ln Vitro |
Only in the presence of the FKBP12-FRB allosteric mode of RMC-5552 was recruitment of FKBP12 seen. At the interface between FKBP12 and the FRB domain of mTOR, the density of RMC-5552 is seen. Through the 4-aminopyrazolo[3,4-d] braid core, the “Manhattan chain” of mTOR, and the 2-aminobenzoxazole to E2190 and K2187 Reply[1], RMC-5552 forms hydrogen connections with the backbone of G2238 and V2240.
|
|---|---|
| ln Vivo |
RMC-5552 (1-10 mg/kg; intraperitoneal injection; once weekly; for 28 days) displayed anti-activity in a mouse MCF-7 human breast cancer xenograft model [1]. RMC-5552 demonstrates anti-activity in mice [1]. PK Parameters in Perfume 1 mg/kg[1] Compound Tmax (h) Cmax (ng/mL) Cmax (μM) AUClast (μg/mL × h) AUClast (μM × h) t1/2 (h) ) 38 RMC-5552 2.0 ± 0.0 5667 ± 1106 3.19 ± 0.62 46 089 ± 5320 25.9 ± 3.0 4.8 ± 0.4
|
| Animal Protocol |
Animal/Disease Models: Female Balb/c nude mice (6-8 weeks old) injected with MCF-7 cells [1]
Doses: 1 mg/kg, 3 mg/kg, 10 mg/kg. Route of Administration: intraperitoneal (ip) injection; once a week; for 28 days Experimental Results: resulted in tumor volume reduction. |
| References | |
| Additional Infomation |
mTORC1 Kinase Inhibitor RMC-5552 is a bi-steric inhibitor of the raptor-mammalian target of rapamycin (mTOR) complex 1 (mTOR complex 1; mTORC1), with potential antineoplastic activity. Upon administration, mTORC1 kinase inhibitor RMC-5552 selectively targets, binds to and inhibits the serine/threonine kinase activity of mTORC1, resulting in decreased expression of mRNAs necessary for cell cycle progression, which may induce cell cycle arrest and tumor cell apoptosis. mTORC1 phosphorylates transcription factors, such as ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which stimulate protein synthesis and regulate cell growth, proliferation, motility, and survival. RMC-5552 is able to suppress the phosphorylation of the tumor suppressor activity of 4EBP1, induces apoptosis and decreases proliferation of mTORC1-expressing tumor cells. mTORC1 is a serine/threonine kinase that is upregulated in certain tumor cell types. It plays an important role in the PI3K/Akt/mTOR signaling pathway, which is often deregulated in cancer cells and promotes cell growth, survival, and resistance to chemotherapy and radiotherapy. Selective mTORC1 inhibition improves the poor clinical tolerability as compared to agents that also cause inhibition of the mTORC2 complex.
|
| Molecular Formula |
C93H136N10O24
|
|---|---|
| Molecular Weight |
1778.13
|
| Exact Mass |
1776.972
|
| CAS # |
2382768-62-7
|
| PubChem CID |
162640850
|
| Appearance |
White to off-white solid powder
|
| LogP |
7
|
| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
30
|
| Rotatable Bond Count |
38
|
| Heavy Atom Count |
127
|
| Complexity |
3460
|
| Defined Atom Stereocenter Count |
16
|
| SMILES |
C1C=C(C)[C@H](C[C@@]2(CC[C@H]([C@@](O)(O2)C(C(N2CCCC[C@@]2([H])C(=O)O[C@]([H])([C@@H](C[C@@H]2CC[C@H]([C@H](OC)C2)OC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)N2CC3=CC=C(CN4N=C(C5C6N=C(N)OC=6C=CC=5)C5C(N)=NC=NC4=5)C=C3CC2)C)C[C@@H](O)[C@@H](C=C([C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)C=CC=1)C)C)=O)=O)C)[H])OC |c:1,t:114,128,130|
|
| InChi Key |
IUTYTXDIGUNPAA-GKVGALOGSA-N
|
| InChi Code |
InChI=1S/C93H136N10O24/c1-59-16-12-11-13-17-60(2)77(113-8)54-71-24-19-65(7)93(112,127-71)86(108)89(109)102-30-15-14-18-73(102)90(110)124-78(55-74(104)61(3)49-64(6)84(107)85(115-10)83(106)63(5)48-59)62(4)50-66-21-25-76(79(52-66)114-9)126-92(111)96-29-33-117-35-37-119-39-41-121-43-45-123-47-46-122-44-42-120-40-38-118-36-34-116-32-28-80(105)101-31-27-68-51-67(20-22-70(68)57-101)56-103-88-81(87(94)97-58-98-88)82(100-103)69-23-26-75-72(53-69)99-91(95)125-75/h11-13,16-17,20,22-23,26,49,51,53,58-59,61-63,65-66,71,73-74,76-79,84-85,104,107,112H,14-15,18-19,21,24-25,27-48,50,52,54-57H2,1-10H3,(H2,95,99)(H,96,111)(H2,94,97,98)/b13-11+,16-12+,60-17+,64-49+/t59-,61-,62-,63-,65-,66+,71+,73+,74-,76-,77+,78+,79-,84-,85+,93-/m1/s1
|
| Chemical Name |
[(1R,2R,4S)-2-methoxy-4-[(2R)-2-[(1R,9S,12S,14R,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,14,18-trihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10,20-tetraoxo-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraen-12-yl]propyl]cyclohexyl] N-[2-[2-[2-[2-[2-[2-[2-[2-[3-[6-[[4-amino-3-(2-amino-1,3-benzoxazol-5-yl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~166.67 mg/mL (~93.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (2.81 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: 5 mg/mL (2.81 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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 | 0.5624 mL | 2.8119 mL | 5.6239 mL | |
| 5 mM | 0.1125 mL | 0.5624 mL | 1.1248 mL | |
| 10 mM | 0.0562 mL | 0.2812 mL | 0.5624 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
