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Fig. 1 · Structure
Cat. No.
A11410
CAS No.
1010085-13-8
Formula
C22H21ClFN3O3S
Mol. Weight
461.9

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MK-5108 (VX-689)

Cat. No. A11410 CAS 1010085-13-8

Aurora A Kinase inhibitor

MK-5108, also known as VX-689, is a competitive inhibitor of the ATP-binding site of aurora A kinase.

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Publications for MK-5108

1 publication citing this product

  1. Wei TW, .et al. , Cancer Res, 2017, Jan 15;77(2):494-508 PMID: 28069801
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Biological Activity

Bioactivity / Mechanism

MK-5108 inhibits Aurora A in biochemical assays. In a comparative ADP-Glo study, its Ki was <0.01 nM for free Aurora A, 0.04 ± 0.008 nM for Aurora A/TPX2(1–43), and 1.49 ± 0.21 nM for Aurora B/INCENP(783–918). The free-enzyme value is an upper bound; the other values are means ± SD. This comparison supports preference for Aurora A under the tested assay conditions, with reduced potency against TPX2-bound Aurora A. [1]

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

Target & Activity

Target Activity Value
Aurora A (Cell-free assay) 0.064 nM

In Vitro Studies

Cellular potency and Aurora A/B selectivity depend on the model and concentration. After 8 h, MK-5108 inhibited LATS2(Ser83) phosphorylation with IC50 values of 610 nM in HeLa, 1800 nM in RPE1 and 1200 nM in U2OS cells. Histone H3(Ser28) labeling was unaffected at 9 µM in HeLa, but the authors reported 80% and 20% inhibition at 15 µM in RPE1 and U2OS, respectively. These substrate readouts limit extrapolation from biochemical potency to cellular selectivity. [1]

In an eleven-line NSCLC panel, 72-hour single-agent MTT responses varied markedly: H358, H1355 and H460 had reported IC50 values of 0.25 µM, whereas H1650 and H727 were annotated >20 µM. These values describe relative growth versus untreated controls; the assay description does not establish a matched DMSO-only comparator. [2]

Biochemical inhibition depends on Aurora kinase complex

Biochemical assay · Purified full-length human Aurora A, Aurora A/TPX2(1–43), and Aurora B/INCENP(783–918). [1]

MK-5108 inhibited Aurora A more potently than Aurora B/INCENP in this assay. The Aurora A value was below the measurement limit; TPX2-bound Aurora A was less sensitive than free Aurora A. These Ki values are assay results, not cellular treatment concentrations.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Full-length human Aurora A kinase activityKi <0.01 nM (upper bound; n = 4)[1]
Full-length human Aurora A with TPX2 residues 1–43Ki 0.04 ± 0.008 nM (mean ± SD; n = 3)[1]
Full-length human Aurora B with INCENP residues 783–918Ki 1.49 ± 0.21 nM (mean ± SD; n = 3)[1]

Literature-Reported Treatment Conditions

Treatment concentration
Dose-response titrations; individual MK-5108 concentration points are not enumerated in the read Methods.
Exposure duration
Aurora A: 2 h; Aurora A/TPX2 and Aurora B/INCENP: 1 h, at 25°C.
Method
ADP-Glo with Kemptide substrate. ATP was set to the measured Km for each enzyme: 35, 3 and 10 µM, respectively. Reactions with and without inhibitor were compared; VX-680 was the panel reference.
Vehicle
DMSO stocks; final DMSO fraction not specified in read Methods.
Reported limits
Exact titration points and lot-specific material analysis not established.
Methods and source locations

Compound reported in the paper: MK-5108; Compound label in the paper: MK-5108

Results concern the authors’ MK-5108 material. Adooq material, lot purity and lot-specific stereochemical/form equivalence were not tested in these papers.

Table 1; Results S2-1; Methods S4-2

Full-length human Aurora A kinase activity: ADP-Glo; IC50 converted to Ki accounting for active enzyme concentration; ATP = Km(ATP). Table 1 n denotes independent dose-response experiments, with triplicate measurements. — Table 1, MK-5108 row and footnote a; Results S2-1; Methods S4-2

Full-length human Aurora A with TPX2 residues 1–43: ADP-Glo; final TPX2 40 nM; ATP 3 µM = Km(ATP); IC50-to-Ki conversion. — Table 1, MK-5108 row; Results S2-1; Methods S4-2

Full-length human Aurora B with INCENP residues 783–918: ADP-Glo; ATP 10 µM = Km(ATP); IC50-to-Ki conversion. — Table 1, MK-5108 row; Results S2-1; Methods S4-2

Cellular Aurora A/B substrate profiling across three cell lines

Cell-based study · HeLa cervical carcinoma, hTERT-RPE1 retinal pigment epithelial and U2OS osteosarcoma cells. [1]

After 8 h, MK-5108 reduced pLATS2(Ser83) with model-dependent potency. Histone H3(Ser28) phosphorylation was spared at 9 µM in HeLa, but was inhibited at 15 µM in RPE1 and U2OS to different extents. Cellular selectivity therefore depends on model and exposure concentration.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
HeLa pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cellsIC50 610 nM[1]
hTERT-RPE1 pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cellsIC50 1800 nM[1]
U2OS pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cellsIC50 1200 nM[1]
pHistone H3(Ser28) labeling, a comparator Aurora B activity readoutEffect at stated concentration HeLa: no effect at 9 µM; RPE1: 80% inhibition at 15 µM; U2OS: 20% inhibition at 15 µM.[1]

Literature-Reported Treatment Conditions

Treatment concentration
Dose-response series; HeLa up to 9 µM and RPE1/U2OS up to 15 µM.
Exposure duration
8 h
Method
Quantitative immunofluorescence for pLATS2(Ser83), pH3(Ser28), MPM2 and DNA; only MPM2-positive mitotic cells analyzed. Readout specificity was checked by Aurora A/B RNAi in Figure 3.
Vehicle
DMSO control; final vehicle percentage not specified in the read Methods.
Reported limits
No confidence intervals for fitted IC50 values. Supplier Table S1 and antibody Table S3 were not acquired as usable files; the main Methods identify the measured phospho-epitopes and imaging controls.
Methods and source locations

Compound reported in the paper: MK-5108; Compound label in the paper: MK-5108

Results concern the authors’ MK-5108 material. Adooq material, lot purity and lot-specific stereochemical/form equivalence were not tested in these papers.

Figures 3–5 and captions; Table 3; Results S2-2/S2-3; Methods S4-7

HeLa pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cells: 8-h fixed-cell immunofluorescence; normalized to DMSO control; four-parameter variable-slope dose-response fit. Points are means across four separate plates, with SD; no IC50 uncertainty is supplied. — Figure 4A; Table 3, MK-5108/HeLa; Methods S4-7

hTERT-RPE1 pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cells: 8-h fixed-cell immunofluorescence; normalized to DMSO control; four-parameter variable-slope dose-response fit. Points are means across four separate plates, with SD; no IC50 uncertainty is supplied. — Figure 5A; Table 3, MK-5108/RPE1; Methods S4-7

U2OS pLATS2(Ser83) labeling intensity in MPM2-positive mitotic cells: 8-h fixed-cell immunofluorescence; normalized to DMSO control; four-parameter variable-slope dose-response fit. Points are means across four separate plates, with SD; no IC50 uncertainty is supplied. — Figure 5A; Table 3, MK-5108/U2OS; Methods S4-7

pHistone H3(Ser28) labeling, a comparator Aurora B activity readout: Directly transcribed Figure 4A/5A annotations and Table 3; these are not pH3 IC50 values. Figure 5A graph annotations denote approximate endpoint inhibition. — Figures 4A and 5A; Table 3, MK-5108 rows

Heterogeneous 72-hour growth responses in NSCLC cells

Cell-based study · Eleven NSCLC lines: H358, H1355, H460, A427, H1666, H1975, A549, Calu-1, HCC827, H1650 and H727. [2]

MTT responses varied substantially across the panel. H358, H1355 and H460 had printed IC50 values of 0.25 µM, while H1650 and H727 were annotated >20 µM. This is a short-term relative-growth endpoint and does not establish direct target engagement or cell killing.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
H358 relative growth measured by MTT, versus untreated controlIC50 0.25 µM[2]
H1355 relative growth measured by MTT, versus untreated controlIC50 0.25 µM[2]
H460 relative growth measured by MTT, versus untreated controlIC50 0.25 µM[2]
A427 relative growth measured by MTT, versus untreated controlIC50 ~0.625 µM[2]
H1666 relative growth measured by MTT, versus untreated controlIC50 ~0.80 µM[2]
H1975 relative growth measured by MTT, versus untreated controlIC50 ~1.5 µM[2]
A549 relative growth measured by MTT, versus untreated controlIC50 ~2.5 µM[2]
Calu-1 relative growth measured by MTT, versus untreated controlIC50 ~10 µM[2]
HCC827 relative growth measured by MTT, versus untreated controlIC50 10–20 µM[2]
H1650 relative growth measured by MTT, versus untreated controlIC50 >20 µM[2]
H727 relative growth measured by MTT, versus untreated controlIC50 >20 µM[2]

Literature-Reported Treatment Conditions

Treatment concentration
0.01–20 µM tested in Methods. IC50 values are assay outputs, not uniform treatment doses.
Exposure duration
72 h
Method
Single-agent MK-5108; MTT compared with untreated control.
Vehicle
MK-5108 dissolved in DMSO and diluted in RPMI medium. The assay description specifies untreated controls; a matched DMSO-only control is not established.
Co-treatment
None in this adopted experiment.
Reported limits
Final DMSO fraction and vehicle matching are not established. Figure 1b axis is displayed through 10 µM, whereas Methods specify testing through 20 µM; >20 µM values are transcribed as author annotations, not independently recalculated.
Methods and source locations

Compound reported in the paper: MK-5108; Compound label in the paper: MK-5108

Results concern the authors’ MK-5108 material. Adooq material, lot purity and lot-specific stereochemical/form equivalence were not tested in these papers.

Methods: Cell lines and reagents; Short-term MTT; Statistical analysis; Results: Anti-proliferative activity; Figure 1b

H358 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H1355 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H460 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

A427 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H1666 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H1975 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

A549 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

Calu-1 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

HCC827 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H1650 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

H727 relative growth measured by MTT, versus untreated control: 72-h MTT. Methods specify six replicates including an untreated control and dose-response curves from triplicate experiments. Values are printed Figure 1b annotations; no fitted-value uncertainty reported there. — Figure 1b printed IC50 list and caption; Methods: Short-term MTT

In Vivo Studies

In an SK-LMS1 xenograft experiment in athymic mice, oral MK-5108 at 30 or 60 mg/kg every 12 h for two consecutive days per week over four weeks reduced mean implant weight versus vehicle (P < 0.05). Tumor TUNEL and phospho-histone H3 staining increased, while Ki-67 staining decreased. Total tumor burden was described only as a trend (P < 0.065; data not shown). The authors reported n = 3, with allocation not explicitly clarified in the Results sentence. [3]

MK-5108 monotherapy in an SK-LMS1 xenograft model

Animal study · SK-LMS1 tumor implants in athymic Fox1 nu/nu mice; Results report n = 3. [3]

Oral MK-5108 lowered mean implant weight and altered tumor histology relative to vehicle. The reported total tumor-burden result was only a trend. Small reported n, unclear allocation and within-animal implant sampling constrain inference.

Measured endpoints — not treatment concentrations
EndpointReported resultReference
Mean implant size expressed as tumor weight; mean of six largest implants per mouseDirection and reported significance Both 30 and 60 mg/kg groups lower than vehicle; P < 0.05 (Figure 5B).[3]
Total tumor burdenAuthor-reported trend P < 0.065; data not shown[3]
Tumor TUNEL, phospho-HH3 and Ki-67 stainingDirection and reported significance TUNEL increased and Ki-67 decreased, with P < 0.05 stars at both doses (Figure 5C/E). Phospho-HH3 increased in direction at both doses, but Figure 5D marks a P < 0.05 star only at 60 mg/kg.[3]

Conditions shared by the study groups

Route
Oral gavage
Frequency
Every 12 h for 2 consecutive days each week
Treatment course
Four weekly treatments, beginning about 2 weeks after xenografting when tumors were palpable.
Vehicle
0.05% methyl cellulose/0.25% SDS; 300 µL gavage volume.
Study groups and reported outcomes
Group / doseComparatorObserved resultReference
MK-5108 30 mg/kgEqual-volume vehicle gavage on the identical schedule.Lower mean implant weight than vehicle control (Figure 5B, P < 0.05). Increased TUNEL-positive cells and phospho-HH3 staining, with reduced Ki-67 staining (Figure 5C–E). Total tumor burden was described only as a trend (P < 0.065; data not shown). Figure 5D does not mark significance for phospho-HH3 at 30 mg/kg; no such claim is adopted.[3]
MK-5108 60 mg/kgEqual-volume vehicle gavage on the identical schedule.Lower mean implant weight than vehicle control (Figure 5B, P < 0.05). Increased TUNEL-positive cells and phospho-HH3 staining, with reduced Ki-67 staining (Figure 5C–E). Total tumor burden was described only as a trend (P < 0.065; data not shown).[3]
MK-5108 30 mg/kg
Model: SK-LMS1 intraperitoneal tumor implants in athymic Fox1 nu/nu mice.
Reported limits: Results state n = 3 without an explicit per-group allocation in that sentence. Figure 5 does not define error-bar semantics. Sex, age, randomization, blinding and a systemic toxicity endpoint are not established in the read animal Methods/caption.
MK-5108 60 mg/kg
Model: SK-LMS1 intraperitoneal tumor implants in athymic Fox1 nu/nu mice.
Reported limits: Results state n = 3 without an explicit per-group allocation in that sentence. Figure 5 does not define error-bar semantics. Sex, age, randomization, blinding and a systemic toxicity endpoint are not established in the read animal Methods/caption.
Methods and source locations

Compound reported in the paper: MK-5108; Compound label in the paper: MK-5108

Results concern the authors’ MK-5108 material. Adooq material, lot purity and lot-specific stereochemical/form equivalence were not tested in these papers.

Methods: Tumor xenografting; Results: MK-5108 monotherapy attenuates SK-LMS1 tumorigenicity in vivo; Figure 5

Mean implant size expressed as tumor weight; mean of six largest implants per mouse: Excision and weighing at end of four weekly courses. No exact means or error magnitudes extracted from graph. — Methods: Tumor xenografting; Figure 5B and caption

Total tumor burden: Authors describe a trend in both dose groups; no claim of P < 0.05 significance for total burden. — Results: MK-5108 monotherapy attenuates SK-LMS1 tumorigenicity in vivo

Tumor TUNEL, phospho-HH3 and Ki-67 staining: Formalin-fixed tumor sections; TUNEL and immunohistochemistry. Multiple implants/fields sampled within each animal; fields are not independent animals. — Methods: Tumor xenografting; Figure 5C–E and caption

MK-5108 30 mg/kg · Methods: Tumor xenografting; Results: MK-5108 monotherapy attenuates SK-LMS1 tumorigenicity in vivo; Figure 5A–E

MK-5108 60 mg/kg · Methods: Tumor xenografting; Results: MK-5108 monotherapy attenuates SK-LMS1 tumorigenicity in vivo; Figure 5A–E

Specifications

Manufacturer Adooq Bioscience
Actions Inhibitor
CAS Number 1010085-13-8
Applications Aurora A Kinase inhibitor
Formula C22H21ClFN3O3S
Molecular Weight 461.9
Synonyms VX689
SMILES
O=C(O)[C@]1(Cc2cccc(Nc3nccs3)n2)CC[C@@H](Oc2cccc(Cl)c2F)CC1

Storage & Solubility

In Vitro Solubility

Reported Solubility

SolventReported Solubility
DMSO 81 mg/mL (175.35 mM)
Water Insoluble
Ethanol Insoluble

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.

In Vivo Preparation

Concentration
28 mg/mL
Vehicle
0.5% methylcellulose+0.2% Tween 80

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] Christian O de Groot, Judy E Hsia, John V Anzola, et al. A Cell Biologist’s Field Guide to Aurora Kinase Inhibitors Frontiers in Oncology (2015). PMID: 26732741 DOI: 10.3389/fonc.2015.00285 Source material
  2. [2] Danielle C Chinn, William S Holland, Philip C Mack. Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies Journal of Cancer Research and Clinical Oncology (2014). PMID: 24756365 DOI: 10.1007/s00432-014-1675-6 Source material
  3. [3] Weiwei Shan, Patricia Y Akinfenwa, Kari B Savannah, et al. A Small-Molecule Inhibitor Targeting the Mitotic Spindle Checkpoint Impairs the Growth of Uterine Leiomyosarcoma Clinical cancer research : an official journal of the American Association for Cancer Research (2012). PMID: 22535157 DOI: 10.1158/1078-0432.CCR-11-3058 Source material

Publications

1 publication citing this product

  1. Wei TW, .et al. , Cancer Res, 2017, Jan 15;77(2):494-508 PMID: 28069801

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