Ridaforolimus (Deforolimus, MK-8669)

Name: Ridaforolimus (Deforolimus, MK-8669)
Brand: Selleck Chemicals
SKU: S1022
Rating: 5 (12 reviews)

For research use only.

Catalog No.S1022 Synonyms: AP23573

12 publications

Ridaforolimus (Deforolimus, MK-8669) Chemical Structure

CAS No. 572924-54-0

Ridaforolimus (Deforolimus, MK-8669, AP23573) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. Phase 3.

Selleck's Ridaforolimus (Deforolimus, MK-8669) has been cited by 12 publications

PLoS Biol, 2019, 17(5):e3000252

PubMed: 31112550 ( click the link to review the publication )

Sci Signal, 2019, 12(589)

PubMed: 31289212 ( click the link to review the publication )

Int J Mol Med, 2019, 43(1):47-56

PubMed: 30387804 ( click the link to review the publication )

Cancer Res, 2018, 78(10):2732-2746

PubMed: 29472518 ( click the link to review the publication )

Int J Oncol, 2018, 52(3):828-840

PubMed: 29344641 ( click the link to review the publication )

Gynecol Oncol, 2016, 141(3):570-9

PubMed: 27017985 ( click the link to review the publication )

Anticancer Res, 2016, 36(11):5765-5771

PubMed: 27793898 ( click the link to review the publication )

Neoplasia, 2015, 17(8):625-33

PubMed: 26408255 ( click the link to review the publication )

J Lipid Res, 2014, 55(5):919-28

PubMed: 24565756 ( click the link to review the publication )

Int J Oncol, 2014, 44(3):959-69

PubMed: 24366069 ( click the link to review the publication )

Neurosci Bull, 2014, 30(1):21-32

PubMed: 24132796 ( click the link to review the publication )

Mol Pharmaco, 2013, 84(1):104-13

PubMed: 23619386 ( click the link to review the publication )

2 Customer Reviews

Breast cancer cells were pretreated with 100ng/ml EGF for 15 min and then treated with the indicated concentrations of Deforolimus for 24 hours.

Dr. Zhang of Tianjin Medical University. Ridaforolimus (Deforolimus, MK-8669) purchased from Selleck.

Protein analysis of ARK1 and ARK2 (A) xenografts following acute therapy with vehicle, ridaforolimus, lapatinib and trastuzumab or the triple combination.

Gynecol Oncol, 2016, 141(3):570-9. Ridaforolimus (Deforolimus, MK-8669) purchased from Selleck.

Purity & Quality Control

Choose Selective mTOR Inhibitors

Biological Activity

Description

Targets

FKBP12 ^[6] ()	mTOR ^[1] (HT-1080 cells)
	0.2 nM

In vitro

Treatment of HT-1080 cells with Deforolimus induces a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC50 of 0.2 nM and 5.6 nM, respectively, and leads to a decrease in cell size, an increase in the proportion of cells in the G1 phase of the cell cycle, and inhibition of glucose uptake. Deforolimus displays significant antiproliferative activity a broad panel of cell lines with EC50 of 0.2-2.3 nM. Deforolimus potently and selectively inhibits VEGF production in a dose-dependent manner. ^[1] Deforolimus treatment significantly induces growth suppression in human NSCLC cell lines with IC30 values of 2.45-8.83 nM, with the exception of H157 with IC30 of >20 nM. Deforolimus treatment (2.8-5.9 nM) significantly dephosphorylates p70S6K^Thr389 in A549, H1703 and H157 cells, except H1666 that may express a resistant variant of mTORC1, and causes increased phosphorylation of pAKT^ser473 and pAKT^Thr308 in A549 and H1703 cells. Deforolimus in combination with the MEK inhibitors, CI-1040 or PD0325901 exhibits dose-dependent synergism in lung cancer cell lines, which is associated with the suppression of proliferation rather than enhancement of cell death, involving the inhibition of ribosomal biogenesis by 40% within 24 hours and a decreased polysome/monosome ratio. ^[2]

In 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]

Protocol

Kinase Assay: ^[1]	- Collapse Cell based target inhibition: HT-1080 cells are treated with increasing concentrations of Deforolimus (0-100 nM) for 2 hours, prior to harvest. Cellular lysates are extracted in denaturing lysis buffer, resolved on SDS-PAGE and transferred to PVDF membranes. After blocking, membranes are incubated with primary antibodies for 1 hour, followed by appropriate HRPconjugated secondary antibodies for 1 hour at room temperature. Immunoreactive proteins are detected using enhanced chemiluminescence and autoradiography performed by exposure to X-ray film. IC50 is determined from the inhibition of levels of phosphorylated ribosomal protein S6 (p-S6) and 4E-BP1 (p-4E-BP1).
Cell Research: ^[2]	- Collapse Cell lines: Colo205, H1755, H1395, H1666, A549, H157, and H1703 cells Concentrations: Dissolved in ethanol, final concentrations ~ 1 μM Incubation Time: 72-120 hours Method: 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). Deforolimus effects are measured using the CellTiter 96 Aqueous nonradioactive cell proliferation assay and Sulforhodamine B assays. For Deforolimus, growth effects are described as IC30 because rapamycin and its derivatives do not significantly impede cell proliferation. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: Male and female athymic NCr-nu mice with xenografts established by subcutaneous implantation of PC-3, A549, HCT-116, MCF7, PANC-1 and SK-LMS-1 tumors Dosages: ~10 mg/kg Administration: Intraperitoneally (Only for Reference)

References

- Collapse

Solubility (25°C)

In vitro	DMSO	198 mg/mL (199.95 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 4% Ethanol+5% Tween 80+5% propylene glycol For best results, use promptly after mixing.	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Ridaforolimus (Deforolimus, MK-8669) SDF

Molecular Weight	990.21
Formula	C₅₃H₈₄NO₁₄P
CAS No.	572924-54-0
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	AP23573
Smiles	CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OP(=O)(C)C)C)C)O)OC)C)C)C)OC

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid 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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

Serial Dilutions
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Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

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Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01431547	Completed	Drug: dalotuzumab\|Drug: ridaforolimus	Solid Tumors	Merck Sharp & Dohme Corp.	February 2012	Phase 1
NCT01431534	Terminated	Drug: Ridaforolimus	Solid Tumors	Merck Sharp & Dohme Corp.	January 30 2012	Phase 1
NCT01380184	Completed	Drug: ridaforolimus	Cancer Advanced	Merck Sharp & Dohme Corp.	July 5 2011	Phase 1
NCT01295632	Completed	Drug: ridaforolimus\|Drug: MK-0752\|Drug: MK-2206	Advanced Cancer	Merck Sharp & Dohme Corp.	February 2011	Phase 1
NCT01212627	Terminated	Drug: Ridaforolimus	Non-Small Cell Lung Cancer	Angela Taber MD\|Rhode Island Hospital\|The Miriam Hospital\|Memorial Hospital of Rhode Island\|Roger Williams Medical Center\|Brown University	September 2010	Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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mTOR Signaling Pathway Map

mTOR Inhibitors with Unique Features

Pan mTOR inhibitor

KU-0063794 : mTORC1 and mTORC2, IC50=~10 nM.
Most Potent mTOR Inhibitor

Rapamycin (Sirolimus) : mTOR, IC50=~0.1 nM.
FDA-approved mTOR Inhibitor

Temsirolimus (CCI-779, NSC 683864) : Approved by FDA for Renal Cell Carcinoma (RCC).
Newest mTOR Inhibitor

XL388 ^New : Highly potent, selective, ATP-competitive inhibitor of mTOR with IC50 of 9.9 nM, 1000-fold selectivity over the closely related PI3K kinases.

Related mTOR Products

MHY1485 ^New

MHY1485 is a potent, and cell-permeable mTOR activator, and also potently inhibits autophagy.
CHIR-99021 (CT99021) ^New

CHIR-99021 (CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 of 10 nM and 6.7 nM, respectively. CHIR99201 does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. CHIR99021 functions as a Wnt/β-catenin activator and induces autophagy.
Dorsomorphin (Compound C) ^New

Dorsomorphin is a potent, reversible, selective AMPK inhibitor with K_i of 109 nM in cell-free assays, exhibiting no significant inhibition of several structurally related kinases including ZAPK, SYK, PKCθ, PKA, and JAK3. Dorsomorphin selectively inhibits the BMP type I receptors ALK2, ALK3 and ALK6. Dorsomorphin is used in promoting specific cell differentiation and inducing cancer cell line autophagy.
Rapamycin (Sirolimus)

Rapamycin (Sirolimus, AY 22989, NSC-2260804) is a specific mTOR inhibitor with IC50 of ~0.1 nM HEK293 cells.
Everolimus (RAD001)

Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM in a cell-free assay. Everolimus induces cell apoptosis and autophagy and inhibits tumor cells proliferation.
AZD8055

AZD8055 is a novel ATP-competitive mTOR inhibitor with IC50 of 0.8 nM in MDA-MB-468 cells with excellent selectivity (∼1,000-fold) against PI3K isoforms and ATM/DNA-PK. AZD8055 induces caspase-dependent apoptosis and also induces autophagy. Phase 1.

Features:First drug to inhibit both types of mTOR protein.
Torin 1

Torin 1 is a potent inhibitor of mTORC1/2 with IC50 of 2 nM/10 nM in cell-free assays; exhibits 1000-fold selectivity for mTOR than PI3K.
Temsirolimus (CCI-779)

Temsirolimus (CCI-779, NSC 683864) is a specific mTOR inhibitor with IC50 of 1.76 μM in a cell-free assay. Temsirolimus induces autophagy and apoptosis.
Sapanisertib (MLN0128)

Sapanisertib (MLN0128, INK 128, TAK-228) is a potent and selective mTOR inhibitor with IC50 of 1 nM in cell-free assays; >200-fold less potent to class I PI3K isoforms, superior in blocking mTORC1/2 and sensitive to pro-invasion genes (vs Rapamycin). Phase 1.
Tacrolimus (FK506)

Tacrolimus (FK506, FR900506, Fujimycin, Prograf) is a 23-membered macrolide lactone, it reduces peptidyl-prolyl isomerase activity in T cells by binding to the immunophilin FKBP12 (FK506 binding protein) creating a new complex. Tacrolimus also inhibits the phosphatase activity of calcineurin. Tacrolimus induces vascular endothelial autophagy.

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Ridaforolimus (Deforolimus, MK-8669)