Kbi110

| Property | Reported Value / Observation | |----------|------------------------------| | | 12 nM (biochemical assay) | | Selectivity panel | >100‑fold selectivity vs. CDK‑1, CDK‑2, CDK‑4/6; modest activity on MAPK‑14 (IC₅₀ ≈ 800 nM) | | Solubility | ~30 µM in DMSO; 5 µM in aqueous buffer (pH 7.4) | | Stability | Stable >48 h at 37 °C in plasma; half‑life ~6 h in mouse liver microsomes | | Cell‑based potency | EC₅₀ ≈ 45 nM in HCT‑116 colon‑cancer cells (p‑Rb dephosphorylation assay) | | In‑vivo PK (mouse) | Oral bioavailability ≈ 38 %; C_max ≈ 2.1 µM; t₁⁄₂ ≈ 3.2 h | | Toxicity | No overt cytotoxicity up to 10 µM in primary hepatocytes; mild weight loss (~5 %) at 50 mg kg⁻¹ d⁻¹ in 28‑day rat study |

| Year | Citation | Key Finding | |------|----------|-------------| | 2019 | Nat. Commun. 10, 4512 | Demonstrated that KBI‑110 reduces phosphorylation of the oncogenic transcription factor in breast‑cancer xenografts. | | 2020 | Cell Reports 31, 107560 | Combined KBI‑110 with a CDK‑12 inhibitor to achieve synthetic lethality in TP53 ‑mutant ovarian cancer. | | 2021 | J. Med. Chem. 64, 11234‑11248 | Published a full SAR (structure‑activity relationship) series, confirming the importance of the 4‑pyridyl substituent for potency. | | 2022 | Science Translational Medicine 14, eabb1234 | Showed that oral KBI‑110 improves motor function in a mouse model of Huntington’s disease via reduced huntingtin aggregation. | | 2023 | Bioorg. Med. Chem. Lett. 53, 128‑133 | Developed a photo‑caged analogue (KBI‑110‑PC) for spatiotemporal control of CDK‑B inhibition in zebrafish embryos. | | 2024 | Nature Chemical Biology 20, 721‑733 | Utilized KBI‑110 in a chemoproteomic screen that identified a previously unknown CDK‑B substrate involved in mitochondrial dynamics. | kbi110

: International markets (outside the US) currently trade at a significant discount, which may favor the fund’s global strategy. Investor Considerations | Property | Reported Value / Observation |

Mara folded the note to her chest and felt an odd, fierce joy. KBI110 had not just cataloged objects; it had learned to place them back into human hands. It had learned a kind of gentle stewardship. KBI110 had not just cataloged objects