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Fig. 1 · Structure
Cat. No.
A10598
CAS No.
957116-20-0
Formula
C31H30ClF2N5O3
Mol. Weight
594.1

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MK 3207 HCl

Cat. No. A10598 CAS 957116-20-0

CGRP Receptor antagonist

MK 3207 hydrochloride is a potent CGRP receptor antagonist with IC50 of 0.12 nM.

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Publications for MK 3207 HCl

2 publications citing this product

  1. Marlene Dallmayer, .et al. , Cell Death Dis, 2019, Feb 11;10(2):116 PMID: 30741933
  2. Marlene Dallmayer, .et al. , bioRxiv, 2018, 2018
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Biological Activity

Bioactivity / Mechanism

Published parent MK-3207 (compound 4) antagonized CGRP-induced cAMP signaling in HEK293 cells expressing human CLR/RAMP1. Functional IC50 values were 0.12 ± 0.05 nM without added human serum and 0.17 ± 0.07 nM in 50% human serum (mean ± SD; n = 6 each). These are functional assay endpoints for the parent compound, not hydrochloride-specific validation or treatment doses. [1]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Target & Activity

Target Activity Value
CGRP 0.12 nM

In Vitro Studies

Adooq-supplied MK-3207 reduced the Resazurin signal in A673 Ewing sarcoma cells after 72 h at 50 and 150 µM; RAMP1 knockdown attenuated the effect at 150 µM. At 20 µM, it also reduced colony formation in A673 and RDES cells versus DMSO controls. These cell-growth findings occur at micromolar concentrations and do not establish direct cytotoxicity or exclusive target specificity. The paper does not specify the supplied salt or lot. [2]

Functional antagonism at human CLR/RAMP1

Cell-based study · HEK293 cells stably expressing human CLR/RAMP1 [1]

MK-3207 inhibited CGRP-induced cAMP production, with a small potency shift in 50% human serum. Table 1 includes telcagepant as an assay comparator.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Inhibition of CGRP-induced cAMP production without added human serumIC50 0.12 ± 0.05 nM (n = 6; mean ± SD)[1]
Inhibition of CGRP-induced cAMP production in 50% human serumIC50 0.17 ± 0.07 nM (n = 6; mean ± SD)[1]

Literature-Reported Treatment Conditions

Method
CGRP-induced cAMP production assay, with and without 50% human serum.
Reported limits
Compound concentration series, agonist concentration, incubation duration, vehicle and normalization controls are not specified in acquired Bell text; assay methodology is cited to earlier work. Six replicates are reported per endpoint; their biological/technical nature is not specified.
Methods and source locations

Compound reported in the paper: MK-3207; Compound label in the paper: Compound 4

Results describe published parent MK-3207; hydrochloride-specific behavior and Adooq lot performance were not established.

Table 1, compound 4 and footnotes a,c,d; accompanying compound 4 pharmacology paragraph

Inhibition of CGRP-induced cAMP production without added human serum: Cell-based cAMP assay — Table 1, compound 4, cAMP IC50 column; footnotes a,c

Inhibition of CGRP-induced cAMP production in 50% human serum: Same functional assay with 50% human serum — Table 1, compound 4, cAMP + HS IC50 column; footnotes a,d

Resazurin response and RAMP1 knockdown control in A673 cells

Cell-based study · A673 Ewing sarcoma cells; A673/TR/shRAMP1_4 cells for the knockdown comparison [2]

MK-3207 reduced the DMSO-normalized Resazurin signal at 50 and 150 µM after 72 h. At 150 µM, doxycycline-induced RAMP1 knockdown attenuated this reduction. This supports target involvement but does not establish exclusive specificity at these high concentrations or directly measure cell death.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
DMSO-normalized Resazurin signal after MK-3207 treatmentQualitative direction and reported significance Reduced at 50 and 150 µM; ***P ≤ 0.001 versus control; mean and SEM, n = 12[2]
Resazurin response to 150 µM MK-3207 with versus without induced RAMP1 knockdownQualitative direction and reported significance Higher normalized signal with RAMP1 knockdown; **P ≤ 0.01; mean and SEM, n = 3[2]

Literature-Reported Treatment Conditions

Treatment concentration
50 and 150 µM in A673; 150 µM in the RAMP1 knockdown comparison.
Exposure duration
72 h drug treatment; Resazurin fluorescence read after a further 7 h indicator incubation.
Method
Resazurin fluorescence normalized to DMSO control. Knockdown comparison used 1 µg/ml doxycycline with versus without induction.
Vehicle
DMSO, with corresponding DMSO-only controls.
Co-treatment
MK-3207 with/without doxycycline-induced RAMP1 knockdown for the mechanistic control; not a two-drug efficacy combination.
Reported limits
Exact final DMSO percentages and whether n denotes independent experiments or wells are not specified. No drug IC50 or direct death measurement is supplied in Fig. 6.
Methods and source locations

Compound reported in the paper: MK-3207; Compound label in the paper: AdooQ Bioscience MK-3207

Adooq-supplied MK-3207 cell results; exact salt and lot applicability remain unverified.

Fig. 6a,b (viewed) and caption; Materials and methods: Small-molecule inhibitor assays; Supplementary Fig. S6, PDF page 5: qRT-PCR validation of shRAMP1_4 in A673 (viewed)

DMSO-normalized Resazurin signal after MK-3207 treatment: Resazurin fluorescence; unpaired two-tailed Student t test — Fig. 6a (viewed), caption and Small-molecule inhibitor assays

Resazurin response to 150 µM MK-3207 with versus without induced RAMP1 knockdown: Resazurin fluorescence; unpaired two-tailed Student t test — Fig. 6b (viewed), caption; Results: Pharmacological inhibition of the CALCB/RAMP1 axis decreases growth of EwS cells

Clonogenic growth under MK-3207 treatment

Cell-based study · A673 and RDES Ewing sarcoma cell colony-formation assays [2]

MK-3207 at 20 µM reduced colony formation relative to DMSO controls in both cell lines. Olcegepant was evaluated in parallel as a separate comparator, not in combination with MK-3207.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Colony formation normalized to DMSO in A673 and RDESQualitative direction and reported significance Reduced in both cell lines; ***P ≤ 0.001 for MK-3207 versus DMSO; mean and SEM, n = 3[2]

Literature-Reported Treatment Conditions

Treatment concentration
20 µM MK-3207; separate comparator 100 µM olcegepant.
Exposure duration
Colonies assessed after 1–3 weeks; inhibitors added 48 h after seeding.
Method
Crystal violet-stained colony counting using ImageJ.
Vehicle
DMSO; DMSO-only control.
Co-treatment
No MK-3207/olcegepant combination.
Reported limits
Cell-line-specific endpoint day, final DMSO percentage and biological/technical nature of n are not specified in the acquired assay method.
Methods and source locations

Compound reported in the paper: MK-3207; Compound label in the paper: AdooQ Bioscience MK-3207

Adooq-supplied MK-3207 cell results; exact salt and lot applicability remain unverified.

Fig. 6c (viewed) and caption; Materials and methods: Small-molecule inhibitor assays

Colony formation normalized to DMSO in A673 and RDES: Colony count; unpaired two-tailed Student t test — Fig. 6c (viewed) and caption; Small-molecule inhibitor assays

In Vivo Studies

Parent MK-3207 showed species- and dose-dependent oral bioavailability. Reported F values were 74% in rats at 10 mg/kg, 67% in dogs at 2 mg/kg and 9% in rhesus monkeys at 2 mg/kg; in monkeys, F increased to 41% at 20 mg/kg. Oral dosing used 1% methocel with intravenous reference dosing in DMSO. These pharmacokinetic findings do not demonstrate therapeutic efficacy or establish hydrochloride-form performance. [1]

Preclinical oral bioavailability of parent MK-3207

Animal study · Rat, dog and rhesus monkey pharmacokinetic comparisons of oral and intravenous compound 4 [1]

Oral bioavailability varied by species and dose. These are pharmacokinetic results, not measures of therapeutic efficacy or safety.

Conditions shared by the study groups

Route
Oral; intravenous reference.
Vehicle
Oral: 1% methocel; intravenous: DMSO.
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
Rat
Oral: 10 and 50 mg/kg; intravenous reference: 2 mg/kg.		Intravenous exposure reference for absolute oral bioavailability.Oral F = 74% at 10 mg/kg and 87% at 50 mg/kg.[1]
Dog
Oral: 2 and 10 mg/kg; intravenous reference: 0.5 mg/kg.		Intravenous exposure reference for absolute oral bioavailability.Oral F = 67% at 2 mg/kg and 87% at 10 mg/kg.[1]
Rhesus monkey
Oral: 2 and 20 mg/kg; intravenous reference: 0.5 mg/kg.		Intravenous exposure reference for absolute oral bioavailability.Oral F = 9% at 2 mg/kg and 41% at 20 mg/kg.[1]
Rat
Model: Rat
Reported limits: n, sex, sampling schedule and dose mass basis (free-base equivalents versus administered mass) are not specified in the acquired table; values are reproduced without conversion.
Dog
Model: Dog
Reported limits: n, sex, sampling schedule and dose mass basis (free-base equivalents versus administered mass) are not specified in the acquired table; values are reproduced without conversion.
Rhesus monkey
Model: Rhesus monkey
Reported limits: n, sex, sampling schedule and dose mass basis (free-base equivalents versus administered mass) are not specified in the acquired table; values are reproduced without conversion.
Methods and source locations

Compound reported in the paper: MK-3207; Compound label in the paper: Compound 4

Results describe published parent MK-3207; hydrochloride-specific behavior and Adooq lot performance were not established.

Table 4 and footnotes a,b; preclinical PK paragraph

Rat · Table 4, rat rows and footnotes a,b

Dog · Table 4, dog rows and footnotes a,b

Rhesus monkey · Table 4, rhesus monkey rows and footnotes a,b

Specifications

Manufacturer Adooq Bioscience
Actions Antagonist
CAS Number 957116-20-0
Applications CGRP Receptor antagonist
Formula C31H30ClF2N5O3
Molecular Weight 594.1
SMILES
C1CCC2(C1)C(=O)N([C@@H](CN2)C3=CC(=CC(=C3)F)F)CC(=O)NC4=CC5=C(C[C@@]6(C5)C7=C(NC6=O)N=CC=C7)C=C4.Cl

Storage & Solubility

In Vitro Solubility

Reported Solubility

No reported solubility data are available for this product.

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

  1. [1] Bell IM, Gallicchio SN, Wood MR, et al. Discovery of MK-3207: A Highly Potent, Orally Bioavailable CGRP Receptor Antagonist ACS medicinal chemistry letters (2010). PMID: 24900170 DOI: 10.1021/ml900016y Source material
  2. [2] Dallmayer M, Li J, Ohmura S, et al. Targeting the CALCB/RAMP1 axis inhibits growth of Ewing sarcoma Cell death & disease (2019). PMID: 30741933 DOI: 10.1038/s41419-019-1372-0 Source material

Publications

2 publications citing this product

  1. Marlene Dallmayer, .et al. , Cell Death Dis, 2019, Feb 11;10(2):116 PMID: 30741933
  2. Marlene Dallmayer, .et al. , bioRxiv, 2018, 2018

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