Ridaforolimus (Deforolimus, MK8669, AP23573)

Alias: AP23573; Deforolimus; MK-8669; AP23573; AP 23573; AP-23573; MK8669; MK 8669; MK-8669; Deforolimus; Ridaforolimus
Cat No.:V0184 Purity: ≥98%
Ridaforolimus (also known as deforolimus, AP-23573; MK-8669) is a novel, potent,investigational and selective mTOR inhibitor withsignificant antitumor effects.
Ridaforolimus (Deforolimus, MK8669, AP23573) Chemical Structure CAS No.: 572924-54-0
Product category: mTOR
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Ridaforolimus (also known as deforolimus, AP-23573; MK-8669) is a novel, potent, investigational and selective mTOR inhibitor ​with potent antitumor properties. Although ridaforolimus is not a prodrug, it inhibits mTOR and FKBP12 similarly to rapamycin, with an IC50 of 0.2 nM in the HT-1080 cell line. A key regulator of protein synthesis, cell proliferation, cell cycle progression, and cell survival, mTOR integrates signals from proteins like PI3K, AKT, and PTEN that are known to play a role in cancer. By preventing cell growth, division, metabolism, and angiogenesis, mTOR inhibition has a starvation-like effect on cancer cells. In a clinical trial for advanced soft tissue and bone sarcoma, it showed promising results.

Biological Activity I Assay Protocols (From Reference)
Targets
FKBP12; mTOR (IC50 = 0.2 nM)
ln Vitro
Deforolimus treatment of HT-1080 cells results in a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC50 values of 0.2 nM and 5.6 nM, respectively. This treatment also causes a reduction in cell size, an increase in the percentage of cells in the G1 phase of the cell cycle, and an inhibition of glucose uptake. Deforolimus exhibits notable antiproliferative activity in a variety of cell lines, with an EC50 range of 0.2–2.3 nM. Deforolimus dose-dependently inhibits the production of VEGF with high potency and specificity. [1] Human NSCLC cell lines with IC30 values of 2.45-8.83 nM with the exception of H157, which has an IC30 of >20 nM, are significantly suppressed in terms of growth when treated with deforolimus. In A549, H1703, and H157 cells, deforolimus treatment (2.8–5.9 nM) significantly dephosphorylates p70S6KThr389 (apart from H1666, which may express a resistant variant of mTORC1) and increases phosphorylation of pAKTser473 and pAKTThr308 in A549 and H1703 cells). In lung cancer cell lines, deforolimus combined with the MEK inhibitors CI-1040 or PD0325901 exhibits dose-dependent synergism that is linked to the suppression of cell proliferation rather than the enhancement of cell death. This is characterized by the inhibition of ribosomal biogenesis by 40% within 24 hours and a decreased polysome/monosome ratio. [2]
ln Vivo
Administration of Deforolimus exerts significant antitumor effects in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas) or A549 (lung) xenografts in a dose-dependent manner, and inhibits mTOR signaling in in SK-LMS-1 xenograft model associated with inhibition of tumor growth.[1]
Enzyme Assay
HT-1080 cells are treated with increasing concentrations of Deforolimus (0-100 nM) for 2 hours, prior to harvest. Denaturing lysis buffer is used to extract cellular lysates, and the resolved samples are then run on SDS-PAGE and transferred to PVDF membranes. Following blocking, primary antibodies are applied to the membranes for 1 hour, followed by secondary antibodies that have been HRP-conjugated for the same amount of time at room temperature. Enhanced chemiluminescence and autoradiography, which involves exposure to X-ray film, are used to identify immunoreactive proteins. The phosphorylation of ribosomal proteins S6 and 4E-BP1 (p-S6 and p-4E-BP1, respectively) is used to calculate the IC50.
Cell Assay
Cells are seeded at 2-3 × 104/mL, and serial dilutions of Deforolimus are added after 2 hours, for at least three cell doublings (72-120 hours). The CellTiter 96 Aqueous Nonradioactive Cell Proliferation Assay and Sulforhodamine B Assays are used to measure the effects of deforolimus. Because rapamycin and its derivatives do not significantly impede cell proliferation, Deforolimus's growth effects are classified as IC30.
Animal Protocol
Mice: Different treatment groups are assigned to animals that have tumors that fall within the acceptable size range. Ridaforolimus is given intravenously (i.p.) on 2 different treatment schedules: (a) daily, 5 days straight every other week; and (b) once per week. The dosages are 3 and 10 mg/kg. The untreated group is the control.
References

[1]. Mol Cancer Ther. 2011 Jun;10(6):1059-71.

[2]. Cancer Res. 2007 Dec 1;67(23):11300-8.

[3]. Anticancer Agents Med Chem. 2012 Feb;12(2):151-62.

[4]. Int J Oncol. 2012 Aug;41(2):425-32.

[5]. Cancer Res. 2012 Sep 1;72(17):4483-93.

[6]. Sci Signal. 2009 Apr 21;2(67):pe24.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C53H84NO14P
Molecular Weight
990.22
Exact Mass
989.5629
Elemental Analysis
C, 64.29; H, 8.55; N, 1.41; O, 22.62; P, 3.13
CAS #
572924-54-0
Appearance
Solid powder
SMILES
C[C@@H]1CC[C@H]2C[C@@H](/C(=C/C=C/C=C\[C@H](C[C@H](C(=O)[C@@H]([C@@H](/C(=C/[C@H](C(=O)C[C@H](OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@@]1(O2)O)[C@H](C)C[C@@H]4CC[C@H]([C@@H](C4)OC)OP(=O)(C)C)C)/C)O)OC)C)C)/C)OC
InChi Key
BUROJSBIWGDYCN-QHPXJTPRSA-N
InChi Code
InChI=1S/C53H84NO14P/c1-32-18-14-13-15-19-33(2)44(63-8)30-40-23-21-38(7)53(61,67-40)50(58)51(59)54-25-17-16-20-41(54)52(60)66-45(35(4)28-39-22-24-43(46(29-39)64-9)68-69(11,12)62)31-42(55)34(3)27-37(6)48(57)49(65-10)47(56)36(5)26-32/h13-15,18-19,27,32,34-36,38-41,43-46,48-49,57,61H,16-17,20-26,28-31H2,1-12H3/b15-13+,18-14-,33-19+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1
Chemical Name
(1R,9S,12S,15R,16E,18R,19R,21R,23S,24Z,26E,28E,30S,32S,35R)-12-[(2R)-1-[(1S,3R,4R)-4-dimethylphosphoryloxy-3-methoxycyclohexyl]propan-2-yl]-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo[30.3.1.04,9]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentone
Synonyms
AP23573; Deforolimus; MK-8669; AP23573; AP 23573; AP-23573; MK8669; MK 8669; MK-8669; Deforolimus; Ridaforolimus
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 Data
Solubility (In Vitro)
DMSO: ~198 mg/mL (~200 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
5% DMSO+40% PEG 300+5% Tween 80+50% H2O: 10mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.0099 mL 5.0494 mL 10.0988 mL
5 mM 0.2020 mL 1.0099 mL 2.0198 mL
10 mM 0.1010 mL 0.5049 mL 1.0099 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.

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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.
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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05364697 Recruiting Device: IoNIR Ridaforolimus-
Eluting Coronary Stent System
Coronary Stenosis
Coronary Disease
Medinol Ltd. August 30, 2022
NCT01380184 Completed Drug: ridaforolimus Cancer, Advanced Merck Sharp & Dohme LLC July 5, 2011 Phase 1
NCT00694083 Completed Drug: Ridaforolimus Neoplasm Merck Sharp & Dohme LLC June 2008 Phase 1
NCT00112372 Completed Drug: Ridaforolimus Cancer Merck Sharp & Dohme LLC May 2005 Phase 1
NCT01010672 Completed Drug: Ridaforolimus Sarcoma Merck Sharp & Dohme LLC November 2009 Phase 2
Biological Data
  • Ridaforolimus (Deforolimus, MK-8669)

    Ridaforolimus attenuates mTOR signaling, resulting in cell shrinkage, cytostatic, and metabolic effects. Mol Cancer Ther, 2011, 10(6), 1059-1071.

  • Ridaforolimus (Deforolimus, MK-8669)

    Ridaforolimus treatment inhibits tumor cell proliferation independent of PTEN status or AKT activation.

  • Ridaforolimus (Deforolimus, MK-8669)

    In vivo activity and efficacy of ridaforolimus. Mol Cancer Ther, 2011, 10(6), 1059-1071.

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