MK-4256

Name: MK-4256
Brand: MedChemExpress
SKU: HY-13466
Rating: 5.0 (2 reviews)

Cat. No.: HY-13466 Purity: 98.01%: FAQs
Data Sheet SDS COA Handling Instructions

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MK-4256 is a potent and selective SSTR3 antagonist with IC₅₀s of 0.66 nM and 0.36 nM in human and mouse receptor binding assays, respectively.

For research use only. We do not sell to patients.

MK-4256 Chemical Structure

CAS No. : 1104599-69-0

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 435	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 435	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 150	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 400	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 640	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 1250	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 2000	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 3000	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 2 publication(s) in Google Scholar

2 Publications Citing Use of MCE MK-4256

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SSTR1 SSTR2 SSTR3 SSTR5 SSTR4

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

MK-4256 is a potent and selective SSTR3 antagonist with IC₅₀s of 0.66 nM and 0.36 nM in human and mouse receptor binding assays, respectively.

IC₅₀ & Target

IC50: 0.66 nM (human SSTR3), 0.36 nM (mouse SSTR3)^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
CHO	IC₅₀	0.36 nM Compound: 8, MK-4256	Displacement of [125I]SS-28 from mouse SSTR3 transfected in CHO cells after 60 to 90 mins Displacement of [125I]SS-28 from mouse SSTR3 transfected in CHO cells after 60 to 90 mins	[PMID: 24900499]
CHO	IC₅₀	0.46 nM Compound: 8, MK-4256	Inhibition of mouse SSTR3 transfected in CHO cells assessed as inhibition of SRIF-induced reduction of cAMP accumulation after 45 mins Inhibition of mouse SSTR3 transfected in CHO cells assessed as inhibition of SRIF-induced reduction of cAMP accumulation after 45 mins	[PMID: 24900499]
CHO	IC₅₀	0.66 nM Compound: 8, MK-4256	Displacement of [125I]SS-28 from human SSTR3 transfected in CHO cells after 60 to 90 mins Displacement of [125I]SS-28 from human SSTR3 transfected in CHO cells after 60 to 90 mins	[PMID: 24900499]
CHO	IC₅₀	0.7 nM Compound: 1, MK-4256	Displacement of [125I]SS-14 from human recombinant SSTR3 expressed in CHO cell membranes incubated for 60 to 90 mins by radioligand binding assay Displacement of [125I]SS-14 from human recombinant SSTR3 expressed in CHO cell membranes incubated for 60 to 90 mins by radioligand binding assay	[PMID: 26005524]
CHO	IC₅₀	0.9 nM Compound: 1, MK-4256	Antagonist activity against human recombinant SSTR3 expressed in CHO cells assessed as reduction in forskolin-induced cAMP accumulation in presence of SS-14 by time-resolved fluorescence assay Antagonist activity against human recombinant SSTR3 expressed in CHO cells assessed as reduction in forskolin-induced cAMP accumulation in presence of SS-14 by time-resolved fluorescence assay	[PMID: 26005524]
CHO	IC₅₀	0.95 nM Compound: 8, MK-4256	Inhibition of human SSTR3 transfected in CHO cells assessed as inhibition of SRIF-induced reduction of cAMP accumulation after 45 mins Inhibition of human SSTR3 transfected in CHO cells assessed as inhibition of SRIF-induced reduction of cAMP accumulation after 45 mins	[PMID: 24900499]
CHO	IC₅₀	2362 nM Compound: 8, MK-4256	Displacement of [125I]SS-28 from human SSTR-1 transfected in CHO cells after 60 to 90 mins Displacement of [125I]SS-28 from human SSTR-1 transfected in CHO cells after 60 to 90 mins	[PMID: 24900499]
CHO	IC₅₀	384 nM Compound: 8, MK-4256	Displacement of [125I]SS-28 from human SSTR-4 transfected in CHO cells after 60 to 90 mins Displacement of [125I]SS-28 from human SSTR-4 transfected in CHO cells after 60 to 90 mins	[PMID: 24900499]
CHO	IC₅₀	4025 nM Compound: 8, MK-4256	Displacement of [125I]SS-14 from human SSTR-2 transfected in CHO cells after 60 to 90 mins Displacement of [125I]SS-14 from human SSTR-2 transfected in CHO cells after 60 to 90 mins	[PMID: 24900499]
CHO	IC₅₀	533 nM Compound: 8, MK-4256	Displacement of [125I]SS-28 from human SSTR-5 transfected in CHO cells after 90 to 120 mins Displacement of [125I]SS-28 from human SSTR-5 transfected in CHO cells after 90 to 120 mins	[PMID: 24900499]
CHO-K1	IC₅₀	0.46 nM Compound: MK-4256	Antagonist activity at mouse SST3 expressed in CHO-K1 cells assessed as inhibition of SRIF-14-induced foreskin-stimulated cAMP accumulation after 45 mins by TR-FRET assay Antagonist activity at mouse SST3 expressed in CHO-K1 cells assessed as inhibition of SRIF-14-induced foreskin-stimulated cAMP accumulation after 45 mins by TR-FRET assay	[PMID: 24944745]
CHO-K1	IC₅₀	0.95 nM Compound: MK-4256	Antagonist activity at human SST3 expressed in CHO-K1 cells assessed as inhibition of SRIF-14-induced foreskin-stimulated cAMP accumulation after 45 mins by TR-FRET assay Antagonist activity at human SST3 expressed in CHO-K1 cells assessed as inhibition of SRIF-14-induced foreskin-stimulated cAMP accumulation after 45 mins by TR-FRET assay	[PMID: 24944745]

In Vitro

MK-4256 has excellent selectivity against other SSTR subtypes based on in vitro assays. In human receptor binding assays, MK-4256 has IC₅₀s >2 μM for SSTR1 and SSTR2. Although the binding IC₅₀ values on SSTR4 and SSTR5 are below 1 μM, there is still >500-fold selectivity. MK-4256 is tested in functional antagonist assays against SSTR4 and SSTR5. The IC₅₀ values are greater than 5 μM (at least 5000-fold selectivity)^[1]. MK-4256 inhibits radiolabeled MK-499 binding of the hERG channel with an IC₅₀=1.74 μM. In a functional patch clamp assay, MK-4256 exhibits 50% blockade of hERG at 3.4 μM concentration^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

MK-4256 reduces glucose excursion in a dose-dependent fashion with maximal efficacy achieves at doses as low as 0.03 mg/kg po. MK-4256 demonstrates exceptional SSTR3-mediated glucose-lowering efficacy in the mouse oGTT model with minimal hypoglycemia risk. MK-4256 achieves complete ablation of glucose excursion (109%) at 1 mg/kg po. MK-4256 reduces the glucose excursion from 0.003 to 10 mg/kg in a dose-dependent manner. The plasma C_max of MK-4256 is determined from parallel mouse PK studies. At 0.01, 0.1, and 1 mg/kg oral dose, MK-4256 achieves C_max of 7, 88, and 493 nM, respectivley^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

494.52

Formula

C₂₇H₂₃FN₈O

CAS No.

1104599-69-0

Appearance

Solid

Color

Light yellow to yellow

SMILES

CN1N=CC([C@@]2(C3=NOC(C)=N3)N[C@@H](C4=NC=C(C5=CC=C(F)C=C5)N4)CC6=C2NC7=C6C=CC=C7)=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : ≥ 100 mg/mL (202.22 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.0222 mL	10.1108 mL	20.2216 mL
5 mM	0.4044 mL	2.0222 mL	4.0443 mL
10 mM	0.2022 mL	1.0111 mL	2.0222 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 3 mg/mL (6.07 mM); Clear solution

This protocol yields a clear solution of ≥ 3 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (30.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 3 mg/mL (6.07 mM); Clear solution

This protocol yields a clear solution of ≥ 3 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (30.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.01%

Select Batch:

Data Sheet (281 KB) SDS (252 KB)

COA (259 KB) LCMS (269 KB)

Handling Instructions (2659 KB)

References

[1]. He S, et al. The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2012 May 7;3(6):484-9. [Content Brief]

[2]. He S, et al. Investigation of Cardiovascular Effects of Tetrahydro-β-carboline sstr3 antagonists. ACS Med Chem Lett. 2014 Apr 21;5(7):748-53. [Content Brief]

Animal Administration
^[1]

Mice^[1]
To demonstrate that the observed glucose lowering by MK-4256 is SSTR3-dependent, the effect of a maximally efficacious dosage of MK-4256 on blood glucose excursion during an oGTT was investigated in SSTR3 KO mice. Administration of MK-4256 (1 mg/kg) and compound A (1 mg/kg; des-F-sitagliptin, a DPP-4 inhibitor included as a positive control) to age-matched C57BL/6N male WT mice significantly inhibits blood glucose excursion by 112 and 91%, respectively.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

[1]. He S, et al. The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes. ACS Med Chem Lett. 2012 May 7;3(6):484-9. [Content Brief]

[2]. He S, et al. Investigation of Cardiovascular Effects of Tetrahydro-β-carboline sstr3 antagonists. ACS Med Chem Lett. 2014 Apr 21;5(7):748-53. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.0222 mL	10.1108 mL	20.2216 mL	50.5541 mL
	5 mM	0.4044 mL	2.0222 mL	4.0443 mL	10.1108 mL
	10 mM	0.2022 mL	1.0111 mL	2.0222 mL	5.0554 mL
	15 mM	0.1348 mL	0.6741 mL	1.3481 mL	3.3703 mL
	20 mM	0.1011 mL	0.5055 mL	1.0111 mL	2.5277 mL
	25 mM	0.0809 mL	0.4044 mL	0.8089 mL	2.0222 mL
	30 mM	0.0674 mL	0.3370 mL	0.6741 mL	1.6851 mL
	40 mM	0.0506 mL	0.2528 mL	0.5055 mL	1.2639 mL
	50 mM	0.0404 mL	0.2022 mL	0.4044 mL	1.0111 mL
	60 mM	0.0337 mL	0.1685 mL	0.3370 mL	0.8426 mL
	80 mM	0.0253 mL	0.1264 mL	0.2528 mL	0.6319 mL
	100 mM	0.0202 mL	0.1011 mL	0.2022 mL	0.5055 mL

MK-4256 Related Classifications

Metabolic Disease Endocrinology

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MK-42561104599-69-0MK4256MK 4256Somatostatin ReceptorSSTRsSSTRInhibitorinhibitorinhibit

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MK-4256

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MK-4256 Related Antibodies

2 Publications Citing Use of MCE MK-4256

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All Somatostatin Receptor Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

MK-4256 Related Antibodies

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Complete Stock Solution Preparation Table

MK-4256 Related Classifications

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