FKBP12
FKBP12 (FKBP1A) is a highly conserved immunophilin that functions as a peptidyl-prolyl cis-trans isomerase and participates in protein folding, intracellular signaling, and calcium homeostasis[1]. Mechanistically, FKBP12 forms regulatory complexes with multiple signaling proteins, including ryanodine receptors, transforming growth factor-β (TGF-β) type I receptors, and the mammalian target of rapamycin (mTOR), thereby linking protein conformational control to signal transduction pathways[1][2]. A key biological process involving FKBP12 is the regulation of intracellular Ca2+ release, where FKBP12 associates with ryanodine receptor channels and contributes to channel gating and calcium signaling dynamics[1][3]. Through its interaction with immunosuppressive ligands, FKBP12 also serves as an essential component of the calcineurin and mTOR signaling pathways; the FKBP12-FK506 complex inhibits calcineurin, whereas the FKBP12-rapamycin complex binds the FKBP-rapamycin-binding domain of mTOR and suppresses mTOR-dependent cellular growth signaling[1][4]. Disease relevance is supported by genetic studies showing that FKBP12 deficiency in mice causes embryonic lethality associated with severe cardiac defects, highlighting its importance in cardiovascular development and calcium signaling regulation[1]. Compared with the closely related isoform FKBP12.6 (FKBP1B), FKBP12 shares structural similarity and regulatory activity toward ryanodine receptors, but FKBP12.6 exhibits distinct channel-specific interactions, particularly in cardiac calcium release systems[1]. For experimental applications, FK506 (tacrolimus) and rapamycin remain the most widely used FKBP12-binding ligands and serve as valuable chemical tools for investigating calcineurin signaling, mTOR regulation, and protein-protein interaction networks[1][4].
References:
- [1]. Tong M, et al. FK506-Binding Proteins and Their Diverse Functions. Curr Mol Pharmacol. 2015;9(1):48-65. [Content Brief]
- [2]. Hoeffer CA, et al. Removal of FKBP12 enhances mTOR-Raptor interactions, LTP, memory, and perseverative/repetitive behavior. Neuron. 2008 Dec 10;60(5):832-45. doi: 10.1016/j.neuron.2008.09.037. PMID: 19081378; PMCID: PMC2630531.
- [3]. Carmody M, et al. FKBP12 associates tightly with the skeletal muscle type 1 ryanodine receptor, but not with other intracellular calcium release channels. FEBS Lett. 2001 Sep 7;505(1):97-102. [Content Brief]
- [4]. Kolos JM, et al. FKBP Ligands-Where We Are and Where to Go? Front Pharmacol. 2018 Dec 5;9:1425. [Content Brief]
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FKBP12 Related Products (40)
Related Products (40)
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KB02-SLF
0 ImagesKB02-SLF is a nuclear FKBP12 covalent PROTAC degrader. KB02-SLF covalently modifies cysteine residues in DCAF16, forms a ternary complex with nuclear FKBP12, and mediates degradation via the CUL4-DDB1 E3 ubiquitin ligase pathway. KB02-SLF promotes polyubiquitination and proteasomal degradation of nucleus-localized FKBP12. KB02-SLF can be used in breast cancer research.
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22-SLF
0 ImagesCat. No.: HY-163807CAS No.: 3079209-82-522-SLF is a PROTAC degrader, that degrades FK506-binding protein 12 (FKBP12) with a DC50 of 0.5 µM. 22-SLF interacts with C227 and C228 in FBXO22 to induce a ternary complex between FKBP12 and FBXO22, and degrades FKBP12 in a FBXO22-dependent manner. 22-SLF can be used for fundamental cancer research as a probe to study the FBXO22 degradation pathway.
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Rapamycin-d3
0 ImagesCat. No.: HY-10219SCAS No.: 392711-19-2Synonyms: Sirolimus-d3; AY-22989-d3; NSC 226080-d3Rapamycin-d3 (Sirolimus-d3; AY-22989-d3; NSC 226080-d3) is the deuterated-labeled Rapamycin (HY-10219). Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC50 of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.
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Rapamycin (GMP Like)
0 ImagesSynonyms: Sirolimus (GMP Like); AY-22989 (GMP Like); NSC 226080 (GMP Like)Rapamycin (Sirolimus) GMP Like is Rapamycin (HY-10219) produced by using GMP like guidelines. GMP Like small molecules works appropriately as an auxiliary reagent for cell therapy manufacture. Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC50 of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.
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Rapamycin-13C,d3
0 ImagesCat. No.: HY-10219S1Synonyms: Sirolimus-13C,d3; AY-22989-13C,d3 NSC 226080-13C,d3Rapamycin-13C,d3 (Sirolimus-13C,d3) is the 13C, deuterated-labeled Rapamycin (HY-10219). Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC50 of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.
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WAY-380153
0 ImagesWAY-380153 (Compound 24) is an FKBP12 inhibitor. WAY-380153 exhibits moderate binding affinity for FKBP12, with a KD of 19 μM (measured by ITC) and 15 μM (measured by NMR). WAY-380153 can be used in research related to neurotrophy and neuroprotection.
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FKBP12 ligand-2
0 ImagesCat. No.: HY-176501CAS No.: 3036243-81-6FKBP12 ligand-2 (compound d) is a high affinity ligand targeting FKBP12. FKBP12 ligand-2 can be used to selectively enhance the binding of heterobifunctional molecules to BRD4, enriching the drug intracellularly through the "CellTrap" effect to form a ternary complex of FKBP12-ligand-BRD4. This ternary complex has inhibitory activity against BRD4, thereby inhibiting the expression of BRD4 target genes (such as MYC) and inducing tumor cell death. FKBP12 ligand-2 can be used for selective cancer research based on differences in intracellular presenter protein levels.
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dTAGV-1-NEG TFA
0 ImagesCat. No.: HY-145514BdTAGV-1-NEG TFA is an inactive FKBP12F36V PROTAC degrader, the diastereomer of dTAGV-1 (HY-145514D), and a heterobifunctional negative control molecule. dTAGV-1-NEG TFA does not degrade any protein.
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10-SLF
0 ImagesCat. No.: HY-173082CAS No.: 2765058-89-510-SLF is an FKBP12 PROTAC degrader. 10-SLF covalently interacts with the cysteine residue of FBXW7R465C, forms a ternary complex with FKBP12, and promotes FBXW7-R465C-dependent proteasomal degradation of FKBP12. 10-SLF can be used for the research of pancreatic cancer.
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FKBP12 ligand-3
0 ImagesCat. No.: HY-176502CAS No.: 3036374-26-9FKBP12 ligand-3 (compound dj) is a high-affinity ligand targeting FKBP12. FKBP12 ligand-3 can be used to selectively enhance the binding of heterobifunctional molecules to BRD4, enriching the drug intracellularly through the "CellTrap" effect to form a ternary complex of FKBP12-ligand-BRD4. This ternary complex has inhibitory activity against BRD4, thereby inhibiting the expression of BRD4 target genes (such as MYC) and inducing tumor cell death. FKBP12 ligand-3 can be used for selective cancer research based on differences in intracellular presenter protein levels.
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BRD4/FKBP12 ligand 1
0 ImagesCat. No.: HY-176477BRD4/FKBP12 ligand 1 is a heterobifunctional BRD4 and FKBP12 (Kd of 0.4 nM) ligand. BRD4/FKBP12 ligand 1 has positive cooperativity in BRD4 binding when pre-bound to FKBP12, and FKBP12-dependent cytotoxicity in cancer cells via the CellTrap effect. BRD4/FKBP12 ligand 1 can be used for the research of acute myeloid leukemia, multiple myeloma, prostate carcinoma.
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MC-25B
0 ImagesCat. No.: HY-170983MC-25B is a DCAF16-recruiting FKBP12 PROTAC degrader with a DC50 of 0.35 μM. MC-25B promotes the formation of a ternary complex with DCAF16 and nuclear-localized FKBP12_NLS, thereby mediating DCAF16-dependent degradation of FKBP12_NLS via the proteasome and Cullin-RING ligase pathway.
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KB03-SLF
0 ImagesCat. No.: HY-147196CAS No.: 2384184-42-1KB03-SLF is a bifunctional PROTAC, formed by conjugating the cysteine-targeting KB03 exploratory fragment with SLF (HY-114872), an FKBP12 ligand that does not support the degradation of FKBP12NLS. KB03-SLF fails to degrade nuclear-localized FKBP12NLS in cells, nor can it mediate the interaction between DCAF16 and FKBP12NLS in a manner similar to KB02-SLF (HY-129610).
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Rapamycin-13C,d3-1
0 ImagesCat. No.: HY-W765245Synonyms: Sirolimus-13C,d3-1; AY-22989-13C,d3-1Rapamycin-13C,d3-1 (Sirolimus-13C,d3-1) is the deuterated, 13C-labeled Rapamycin (HY-10219). Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC50 of 0.1 nM in HEK293 cells. Rapamycin is a molecular glue that binds FKBP12 and mTOR proteins together, thereby inhibiting mTOR kinase activity. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1. Rapamycin is an autophagy activator, an immunosuppressant.
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MP-010
0 ImagesCat. No.: HY-172152CAS No.: 3024617-59-9MP-010 is a FKBP12 ligand that regulates cytosolic calcium by stabilizing RyR channel activity. MP-010 promotes functional improvement in SOD1G93A amyotrophic lateral sclerosis (ALS) mice, as evidenced by improved motor coordination, increased integrity of neuromuscular junctions, and significantly enhanced survival of spinal motor neurons. MP-010 can be used for research in the field of neurological diseases.
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AP1867-NH-PEG3-acid
0 ImagesCat. No.: HY-181500CAS No.: 3132225-36-3
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dTAG-Fluorescein
0 ImagesCat. No.: HY-183439CAS No.: 2365116-48-7dTAG-Fluorescein is a dTAG-class PROTAC conjugated with fluorescein. dTAG-Fluorescein is applicable to homogeneous time-resolved fluorescence (HTRF) competitive displacement binding assays to detect binding affinity with His-FKBP12F36V. dTAG-Fluorescein can recruit VHL or CRBN E3 ligase complexes, thereby specifically driving the selective degradation of FKBP12F36V-tagged proteins, with very limited activity against FKBP12WT and IKZF1.
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