ADT-007 (0.1-600 nM; 3 days) effectively inhibited the viability of KRASG12C mutant MIA PaCa-2 PDAC cells in vitro, with an IC50 value of 3.06 nM[1]. ADT-007 (0.1-600 nM; 3 days) effectively inhibited the viability of sotorasib/adagrasib resistant KRASG12C mutant MIA-AMG-R PDAC cells in vitro, with an IC50 value of 15.59 nM[1]. ADT-007 (5-10 nM; 2 weeks) effectively inhibited the clonogenic formation of KRASG12C mutant MIA PaCa-2 PDAC cells at concentrations as low as 5 nM[1]. ADT-007 (5-10 nM; 2 weeks) effectively inhibited colony formation of sotorasib/adagrasib-resistant KRASG12C mutant MIA-AMG-R PDAC cells at concentrations as low as 5 nM in vitro [1]. ADT-007 also exhibited growth inhibitory activity against MRTX1133-resistant KRASG12D mutant AsPC-1 PDAC cells in vitro [1].

ADT-1004 (10-50 mg/kg; orally; once or twice daily, 5 days a week for 27 consecutive days) showed significant antitumor activity in orthotopic mouse models of pancreatic ductal adenocarcinoma (PDAC) (KPC-luc and 2838c3-luc) [1]. ADT-1004 (40 mg/kg; orally; once daily, 5 days a week for 28 consecutive days) inhibited tumor growth, reduced the levels of activated RAS and pERK, and caused macrophages in the tumor microenvironment of orthotopic KRASG12D mutant pancreatic ductal adenocarcinoma in C57BL/6J mice to transform into the M1 phenotype [1]. ADT-1004 (40 mg/kg; orally; once daily, 5 times a week) inhibited tumor growth in subcutaneous KRASG12D, KRASG12C, KRASG12V and KRASG13Q pancreatic ductal adenocarcinoma PDX models in NSG mice, weakened the pERK signaling pathway, reduced stromal αSMA expression, and reduced tumor cell proliferation [1]. ADT-1004 (40 mg/kg; orally; once daily for 5 days a week for 31 days) inhibited tumor growth in NSG mice with parental and Sotorasib/Adagrasib-resistant KRASG12C mutant pancreatic ductal adenocarcinoma and reduced their pERK levels [1].

Animal/Disease Models:C57BL/6J[1]
Doses: 10 mg/kg; 20 mg/kg; 30 mg/kg; 40 mg/kg; 50 mg/kg
Route of Administration: Oral; once daily; five times a week; for 27 days
Experimental Results: Tumor bioluminescence intensity was reduced in all dose groups compared to the carrier. Tumor weight was significantly reduced in the 20–50 mg/kg dose groups compared to the carrier or the 10 mg/kg dose group. The mean plasma concentrations of the active metabolite ADT-007 were 3.4 nM (20 mg/kg), 5.7 nM (30 mg/kg), 31.2 nM (40 mg/kg), and 54.1 nM (50 mg/kg) 6 hours after the last administration. There was no significant difference in body weight between the treatment and control groups.

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Animal/Disease Models:C57BL/6J[1]
Doses: 40 mg/kg
Route of Administration: Oral; once daily; five times a week; for 27 days
Experimental Results: Compared with the vector group, tumor bioluminescence and tumor weight were significantly reduced. The level of activated RAS-GTP in the tumor was significantly reduced, and the pERK level was reduced by approximately 60% compared to the vector group. The density of F4/80+ macrophages in the tumor microenvironment was reduced, CD206 (M2 marker) expression on F4/80+ macrophages was reduced, MHCII expression on F4/80+ macrophages was reduced, and the M1/M2 macrophage ratio was increased.

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Animal/Disease Models:C57BL/6J (female) [1]
Doses: 20 mg/kg (once daily); 20 mg/kg (twice daily); 40 mg/kg (once daily)
Route of Administration: Oral; 5 times per week
Experimental Results: In all dosing regimens, tumor bioluminescence and tumor weight were significantly reduced compared to the vector group. There was no significant difference in body weight compared to the vector group. Compared to the vector group, the level of activated RAS-GTP in the tumor was reduced by approximately 70%, and the level of pERK was reduced by approximately 60%. The tumor microenvironment exhibited increased densities of CD4+ T cells, CD4+ FoxP3+ Treg cells, CD4+ PD-1+ T cells, CD4+ CTLA4+ T cells, CD8+ T cells, CD8+ PD-1+ T cells, CD8+ CTLA4+ T cells, and CD8+ PD-1+ CTLA4+ LAG3+ CD44+ exhausted T cells. Increased dendritic cell dendritic cells, cDC1 dendritic cells, F4/80+ Ly6G+ granulocytic myeloid-derived suppressor cells (MDSCs), and F4/80+ macrophages with upregulated MHCII expression and downregulated CD206 expression were also observed.

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Animal/Disease Models:NSG[1]
Doses: 40 mg/kg
Route of Administration: Oral; once daily; five times weekly
Experimental Results: Compared with the vector, tumor volume and final tumor weight were significantly reduced in all four KRAS mutation (G12D, G12C, G12V, G13Q) PDX models. Body weight was not significantly different compared with the vector. IHC analysis showed that pERK level, αSMA expression and Ki-67 proliferation marker level were significantly reduced in the treatment group tumors compared with the vector. Compared with the vector, tumor volume and final tumor weight were significantly reduced in the parental KRASG12C MIA PaCa-2 tumors, and pERK level was significantly reduced. Compared with the vector group, this study significantly reduced tumor volume and final tumor weight in KRASG12C MIA-AMG-R tumors resistant to sotoprazib/adagraxib, and significantly reduced pERK levels; neither sotoprazib nor adagraxib showed efficacy in this resistance model. No significant changes in body weight were observed between the treatment group and the vector group.

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Animal/Disease Models:NSG (male) [1]
Doses: 40 mg/kg
Route of Administration: Oral; once daily; 5 times a week; 31 days
Experimental Results: No significant effect was observed on tumor volume or final tumor weight compared to the control group. No significant changes in body weight were observed compared to the control group.

[1]. ADT-1004: a first-in-class, oral pan-RAS inhibitor with robust antitumor activity in preclinical models of pancreatic ductal adenocarcinoma. Mol Cancer. 2025;24(1):76. Published 2025 Mar 13.

C33H36FN3O6

589.65

1945941-72-9

Light yellow to yellow solid

O=C(NCC1=CC=CO1)CC2=C(C)/C(C3=CC=C(F)C=C32)=C/C4=CC(OC)=C(C(OC)=C4)OC(NC5CCN(CC5)C)=O

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~4.17 mg/mL (~7.07 mM; with sonication)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)