CML-07-119
CML-07-119 is a selective GGPPS inhibitor (IC50 27 nM). CML-07-119 induces ER stress, unfolded protein response/XBP1 splicing, and Apoptosis, and modulates ERK/AKT phosphorylation. CML-07-119 reduces serum M protein and shows anti-myeloma effects in mice. CML-07-119 can be used for research on acute myeloid leukemia, pancreatic ductal adenocarcinoma, and colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 2241548-12-7
- Formula: C21H19FN4O8P2S
- Molecular Weight:568.41
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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Help & FAQs
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| RPMI-8226 | EC50 |
90 nM
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Antiproliferative activity against human RPMI-8226 multiple myeloma cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human RPMI-8226 multiple myeloma cells assessed as viability reduction incubated 72 hrs by MTS assay.
|
35077178 |
| RPMI-8226 | EC50 |
144 nM
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Antiproliferative activity against human RPMI-8226 multiple myeloma cells assessed as viability reduction by MTS assay in a separate parallel run.
Antiproliferative activity against human RPMI-8226 multiple myeloma cells assessed as viability reduction by MTS assay in a separate parallel run.
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35077178 |
| KMS-11 | EC50 |
205 nM
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Antiproliferative activity against human KMS11 multiple myeloma cells assessed as viability reduction by MTS assay.
Antiproliferative activity against human KMS11 multiple myeloma cells assessed as viability reduction by MTS assay.
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35077178 |
| JJN-3 | EC50 |
507 nM
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Antiproliferative activity against human JJN3 multiple myeloma cells assessed as viability reduction by MTS assay.
Antiproliferative activity against human JJN3 multiple myeloma cells assessed as viability reduction by MTS assay.
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35077178 |
| MOLM-13 | IC50 |
32 nM
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Antiproliferative activity against human MOLM-13 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human MOLM-13 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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42917932 |
| Kasumi 1 | IC50 |
290 nM
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Antiproliferative activity against human Kasumi-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human Kasumi-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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42917932 |
| NB-4 | IC50 |
80 nM
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Antiproliferative activity against human NB4 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human NB4 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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42917932 |
| MV4-11 | IC50 |
222 nM
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Antiproliferative activity against human MV-4-11 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human MV-4-11 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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42917932 |
| NOMO-1 | IC50 |
110 nM
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Antiproliferative activity against human NOMO-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human NOMO-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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42917932 |
| THP-1 | IC50 |
>10 μM
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Antiproliferative activity against human THP-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay; IC50 >10 μM with only approximately 30% decrease at 10 μM.
Antiproliferative activity against human THP-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay; IC50 >10 μM with only approximately 30% decrease at 10 μM.
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42917932 |
| NOMO-1 | EC50 |
110 nM
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Antiproliferative activity against human NOMO-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
Antiproliferative activity against human NOMO-1 AML cells assessed as viability reduction incubated 72 hrs by MTS assay.
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41510247 |
In Vitro
CML-07-119 (0.1 nM-10 μM; 72 hours) blocks RPMI-8226 cell proliferation with an EC50 of 90 nM[3].
CML-07-119 blocks MIA PaCa-2 cell viability with an EC50 of 1,300 nM[3].
CML-07-119 blocks HCT 116 cell viability with an EC50 of 580 nM[3].
CML-07-119 (1 μM; 72 h) reduces the viability of ccmT4 tumor organoids, while normal N (10128) organoids remain relatively nontoxic[3].
CML-07-119 inhibits RPMI-8226 cell proliferation with an EC50 of 90 nM[4].
CML-07-119 exhibits potent anti-leukemic activity in TP53-mutant AML[5].
CML-07-119 inhibits hFPPS with an IC50 of 1.3 μM, showing selectivity for hGGPPS over hFPPS[1].
CML-07-119 is metabolically stable in mouse and rat liver microsomes[1].
CML-07-119 is a GGSI that exhibits strong affinity for GGDPS relative to FDPS in enzyme affinity evaluations[4].
CML-07-119 inhibits GGPPS catalytic turnover with an IC50 of approximately 27 nM and approximately 50-fold selectivity over FPPS[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MOLM-13 AML cells
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Concentration:500 nM; 500 nM + 10 µM GGOH
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Incubation Time:72 h
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Result:At 500 nM, Q2 was 46.0% and Q3 was 35.6%.
With 10 µM GGOH co-incubation, Q2 was 3.90% and Q3 was 4.56%.
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Cell Line:NOMO-1-Luc AML cells
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Concentration:500 nM; 500 nM + 10 µM GGOH
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Incubation Time:72 h
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Result:At 500 nM, Q2 was 41.3% and Q3 was 8.92%.
With 10 µM GGOH co-incubation, Q2 was 4.07% and Q3 was 0.65%.
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Cell Line:RPMI-8226 multiple myeloma cells
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Concentration:0.1 nM to 10 μM
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Incubation Time:72 h
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Result:Blocked RPMI-8226 cell proliferation with an EC50 of 90 nM.
Parmacokinetics
| Species | Dose | Route | AUC0-t | AUC0-∞ | CLplasma | Vdss | MRT | T1/2 |
|---|---|---|---|---|---|---|---|---|
| Rat[1] | 3 mg/kg | i.v. | 149.4 μM·h | 155.2 μM·h | 0.567 mL/min/kg | 0.211 L/kg | 6.21 h | 5.34 h |
In Vivo
CML-07-119 reduces serum M protein levels and interrupts Rap1a prenylation in transgenic mice[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ (NSG; male and female; 8 weeks old)[2]
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Dosage:3 mg/kg (3 times per week for 12 doses); 3 mg/kg (single dose 16 h before day-38 collection)
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Administration:i.p.; 3 times per week for 12 doses; single dose 16 h before day-38 bone marrow and splenocyte collection
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Result:Tumor burden was significantly lower than PBS controls, measured by total bioluminescence radiance (dorsal + ventral) (p = 0.020).
No strong disease rebound was observed after dosing discontinuation.
Unprenylated RAP1A was increased in bone marrow and splenocyte lysates compared with PBS controls, confirming in vivo GGPPS inhibition.
Chemical Information
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CAS No. 2241548-12-7
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Molecular Weight 568.41
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Formula C21H19FN4O8P2S
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SMILES
O=C(C1=CC=CC(C2=NC(NC(P(O)(O)=O)P(O)(O)=O)=C3C=CSC3=N2)=C1)NC4=CC=C(C(F)=C4)OC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Lee HF, et al. Synthesis and Evaluation of Structurally Diverse C-2-Substituted Thienopyrimidine-Based Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase. Journal of medicinal chemistry. 2022 Feb 10;65(3):2471-2496. [Content Brief]
[3]. Boutin R, et al. Discovery and evaluation of C6-substituted pyrazolopyrimidine-based bisphosphonate inhibitors of the human geranylgeranyl pyrophosphate synthase and evaluation of their antitumor efficacy in multiple myeloma, pancreatic ductal adenocarcinoma, and colorectal cancer. Journal of medicinal chemistry. 2023 Dec 14;66(23):15776-800. [Content Brief]
[4]. Haney SL, et al. Targeting the Isoprenoid Biosynthetic Pathway in Multiple Myeloma. International journal of molecular sciences. 2022 Dec 21;24(1):111. [Content Brief]
[5]. Lagunas-Rangel FA, et al. Cholesterol Reprogramming in Acute Myeloid Leukemia: Integrating Tumor-Intrinsic Metabolism and Immune Crosstalk. Diseases (Basel, Switzerland). 2026 Jul 07;14(7):246. [Content Brief]
[6]. Torcasio R, et al. Lipid metabolic vulnerabilities of multiple myeloma. Clinical and experimental medicine. 2023 Nov;23(7):3373-3390. [Content Brief]
[7]. Tsantrizos Y, et al. Structural and Functional Analysis of GGPPS Inhibition as a Therapeutic Mechanism for Acute Myeloid Leukemia (AML). Research Square. 2025 Dec 17:rs-3. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CML-07-119 Related Classifications
HY-186013 Related Classifications
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