BAY-1895344

SKU: orb1225837

Description

BAY-1895344 is a potent, selective, orally active ATR inhibitor with low-nanomolar potency; potently inhibits the proliferation of a broad spectrum of human tumor cell lines with mean IC50 of 78 nM; inhibits hydroxyurea-induced H2AX phosphorylation, exhibits strong in vivo anti-tumor efficacy in monotherapy in a variety of xenograft models.Blood Cancer,Phase 1 Clinical(In Vitro):Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC50 of 78 nM.Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM).Elimusertib shows good selectivity against mTOR (ratio of IC50 values: mTOR/ATR 61).Elimusertib reveals high selectivity against other related kinases, such as DNA-PK (IC50: 332 nM), ATM (IC50: 1420 nM), and PI3K (IC50: 3270 nM).Elimusertib has potent antiproliferative activity against various cancer cell lines in vitro, 25 for example in the CRC cell lines HT-29 (IC50: 160 nM) and LoVo (IC50: 71 nM), and in the B-cell lymphoma cell line SU-DHL-8 (IC50: 9 nM).\n(In Vivo):Elimusertib shows potent anti-tumor efficacy in monotherapy in a variety of xenograft models of ovarian and colorectal cancer, and causes complete tumor remission in mantle cell lymphoma models.Elimusertib (50 mg/kg; p.o.; b.i.d.; 3 days on/4 days off; for 11 days) exhibits strong antitumor efficacy in the ATM-mutated SU-DHL-8 (ATM K1964E) human GCB-DLBCL cell line derived xenograft model in mice.Elimusertib (20 mg/kg, and 10 mg/kg from day 14; p.o.; daily; 2 days on/5 days off; for 42 days) in combination with Carboplatin (40 mg/kg; i.p.; daily; 1 day on/6 days off) results in synergistic antitumor activity in the platinum-resistant ATM protein low expressing CR5038 human CRC PDX model in NOD/SCID mice.Elimusertib exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg).Elimusertib exhibits terminal elimination half-lives (mouse 0.17 h, rat 1.3 and, dog 1.0 h) due to plasma clearance (3.5, 1.2, and 0.79 L/h/kg respectively) following intravenous administration (mouse, rat and dog 0.3-0.5 mg/kg).

Key Properties

• CAS Number: 1876467-74-1
• MW: 375.436
• Purity: >98% (HPLC)
• Formula: C₂₀H₂₁N₇O
• SMILES: CC1COCCN1C2=NC3=C(C=CN=C3C4=CC=NN4)C(=C2)C5=CC=NN5C
• Target: ATM/ATR
• Solubility: In Vitro: DMSO : 5.4 mg/mL (14.38 mM)

Bioactivity

• In Vivo:
  Elimusertib shows potent anti-tumor efficacy in monotherapy in a variety of xenograft models of ovarian and colorectal cancer, and causes complete tumor remission in mantle cell lymphoma models. Elimusertib (50 mg/kg; p.o. ; b. i. d. ; 3 days on/4 days off; for 11 days) exhibits strong antitumor efficacy in the ATM-mutated SU-DHL-8 (ATM K1964E) human GCB-DLBCL cell line derived xenograft model in mice. Elimusertib (20 mg/kg, and 10 mg/kg from day 14; p.o. ; daily; 2 days on/5 days off; for 42 days) in combination with Carboplatin (40 mg/kg; i.p.; daily; 1 day on/6 days off) results in synergistic antitumor activity in the platinum-resistant ATM protein low expressing CR5038 human CRC PDX model in NOD/SCID mice. Elimusertib exhibits moderate oral bioavailability (rat 87%, dog 51%) following oral administration (rat and dog 0.6-1 mg/kg). Elimusertib exhibits terminal elimination half-lives (mouse 0.17 h, rat 1.3 and, dog 1.0 h) due to plasma clearance (3.5, 1.2, and 0.79 L/h/kg respectively) following intravenous administration (mouse, rat and dog 0.3-0.5 mg/kg). Animal model: Female C. B-17 SCID mice, SU-DHL-8 GCB-DLBCL xenograft model. Dosage: 50 mg/kg. Administration: Oral administration, b. i. d. , 3 days on/4 days off, for 11 days. Result: Inhibited tumor area. Animal model: Male Wistar rats. Dosage: 0.3-0.5 mg/kg for i. v. ; 0.6-1 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous injection and oral administration. Result: Oral bioavailability (87%), T1/2 (1.3 h). Animal model: Female beagle dogs. Dosage: 0.3-0.5 mg/kg for i. v. ; 0.6-1 mg/kg for oral (Pharmacokinetic Analysis). Administration: Intravenous injection and oral administration. Result: Oral bioavailability (51%), T1/2 (1.0 h).
• In Vitro:
  Elimusertib potently inhibits the proliferation of a broad spectrum of human tumor cell lines with a median IC50 of 78 nM. Elimusertib potently suppresses hydroxyurea-induced H2AX phosphorylation (IC50: 36 nM). Elimusertib shows good selectivity against mTOR (ratio of IC50 values: mTOR/ATR 61). Elimusertib reveals high selectivity against other related kinases, such as DNA-PK (IC50: 332 nM), ATM (IC50: 1420 nM), and PI3K (IC50: 3270 nM). Elimusertib has potent antiproliferative activity against various cancer cell lines in vitro, 25 for example in the CRC cell lines HT-29 (IC50: 160 nM) and LoVo (IC50: 71 nM), and in the B-cell lymphoma cell line SU-DHL-8 (IC50: 9 nM).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

BAY 1895344 | BAY1895344

Quick Database Links

Gene Symbol

ATM/ATR