The TGF-β superfamily comprises TGF-βs, bone morphogenetic proteins (BMPs), activins and related proteins. These proteins were identified mainly through their roles in development; they regulate the establishment of the body plan and tissue differentiation through their effects on cell proliferation, differentiation and migration. There are eight vertebrate Smads: Smad1 to Smad8. Smad2 and Smad3 are activated through carboxy-terminal phosphorylation by the TGF-b and activin receptors TbRI and ActRIB, whereas Smad1, Smad5 and Smad8 are activated by ALK-1, ALK-2, BMP-RIA/ALK-3 and BMP-RIB/ALK-6 in response to BMP1–4 or other ligands.

TGF-β binds two receptor types, the TGF-β type I and type II receptors (TβRI and TβRII, respectively) to form the active signaling complex. The TβRII activates TβRI kinase activity by phosphorylating the TβRI, which then transmits the signal intracellularly by phosphorylating the Smad transcription factors. The Smads constitutively shuttle between the cytoplasm and nucleus, but signaling causes the Smads to accumulate predominantly in the nucleus where they bind DNA and other transcriptional machinery to regulate the expression of target genes. TGF-β also involves in the regulations of PI3K and MAPK signaling pathways.

Abnormalities of the TGF-beta receptors and SMADs have been detected in various tumors, including colorectal cancers and pancreatic cancers. In addition, TGF-β/BMP signaling is also involved in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption ofTGF-β/BMP signaling.

References:
[1] Derynck R, et al. Nature. 2003 Oct 9;425(6958):577-84.
[2] Clarke DC, et al. Trends Cell Biol. 2008 Sep;18(9):430-42.
[3] Wu M, et al. Bone Res. 2016 Apr 26;4:16009.


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O-Desmethyl Midostaurin

O-Desmethyl Midostaurin (CGP62221; O-Desmethyl PKC412) is the active metabolite of Midostaurin (HY-10230) via cytochrome P450 liver enzyme metabolism. O-Desmethyl Midostaurin can be used as an indicator for Midostaurin metabolism in vivo[1]. Midostaurin is a multi-targeted protein kinase inhibitor with IC50 ranging from 22-500 nM.

  • CAS Number: 740816-86-8
  • MF: C34H28N4O4
  • MW: 556.61
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Livmoniplimab

Livmoniplimab (ABBV-151; ARGX-115) is a potent humanized anti-LRRC32 (GARP)/TGFβ1 monoclonal antibody. Livmoniplimab blocks LRRC32-mediated activation of latent TGFβ1. Livmoniplimab has the potential for the research of cancer[1].

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine

(S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine is a dual target PROTAC that can not only target to the ubiquitination and degradation of Smad3 but also improve the HIF-α protein level. (S,R,S)-AHPC-C2-amide-benzofuranylmethyl-pyridine has a multi-path anti-fibrosis function and a renal protection function for research of renal anemia[1].

  • CAS Number: 2347517-69-3
  • MF: C41H46N6O6S
  • MW: 750.91
  • Catalog: HIF/HIF Prolyl-Hydroxylase
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

TGFβ-IN-2

TGFβ-IN-2 (Compound 9d) inhibits TGF-β-induced total collagen accumulation in NRK-49F cells with the IC50 of 4.31 μM. TGFβ-IN-2 suppresses the TGF-β-induced protein expression of COL1A1, α-SMA, and p-Smad3 in vitro. TGFβ-IN-2 can be used as a potential effective compound for anti-fibrosis in vivo by oral administration[1].

  • CAS Number: 2387678-02-4
  • MF: C22H22N2O4
  • MW: 378.42
  • Catalog: TGF-beta/Smad
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-Leu-Ser-Lys-Leu-NH2 trifluoroacetate salt

LSKL, Inhibitor of Thrombospondin (TSP-1) is a peptide derived from the latency-associated peptide, inhibits thrombospondin (TSP-1) activation of TGF-β and prevents the progression of hepatic damage and fibrosis.

  • CAS Number: 283609-79-0
  • MF: C21H42N6O5
  • MW: 458.595
  • Catalog: Peptides
  • Density: 1.1±0.1 g/cm3
  • Boiling Point: 817.8±65.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 448.4±34.3 °C

Galunisertib (LY2157299)

Galunisertib (LY2157299) is a selective TGF-β receptor inhibitor with an IC50 of 56 nM.

  • CAS Number: 700874-72-2
  • MF: C22H19N5O
  • MW: 369.419
  • Catalog: TGF-β Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: 619.0±55.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 328.2±31.5 °C

PKCβII Peptide Inhibitor I

PKCβII Peptide Inhibitor I is a PKCβII inhibitor. PKCβII Peptide Inhibitor I shows cardioprotective effects in rat cardiac Ischemia/reperfusion injury model. PKCβII Peptide Inhibitor I also prevents vascular endothelial dysfunction[1].

  • CAS Number: 862502-26-9
  • MF: C61H94N12O19
  • MW: 1299.47000
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

ITD-1

ITD-1 is the first selective TGFβ inhibitor with an IC50 of 460 nM.

  • CAS Number: 1099644-42-4
  • MF: C27H29NO3
  • MW: 415.52
  • Catalog: TGF-β Receptor
  • Density: 1.4±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

WF-536

WF-536 is an orally active inhibitor of Rho-associated coiled-coil-containing protein kinase (ROCK). WF-536 has tumor anti-metastatic activity. WF-536 can be used for the research of cancer[1].

  • CAS Number: 539857-64-2
  • MF: C14H16ClN3O
  • MW: 277.75
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rock-in-d2

ROCK-IN-D2 is an effective and selective inhibitor of ROCK.

  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Pentanoic acid

Pentanoic acid, a short-chain fatty acid, is a product of bacterial metabolism and are associated with allergic skin disorders. Pentanoic acid activates ROCK signaling pathway.

  • CAS Number: 109-52-4
  • MF: C5H10O2
  • MW: 102.132
  • Catalog: ROCK
  • Density: 1.0±0.1 g/cm3
  • Boiling Point: 185.3±3.0 °C at 760 mmHg
  • Melting Point: −20-−18 °C(lit.)
  • Flash Point: 88.9±0.0 °C

Y-39983 HCl

Y-33075 dihydrochloride is a selective ROCK inhibitor derived from Y-27632, and is more potent than Y-27632, with an IC50 of 3.6 nM.

  • CAS Number: 173897-44-4
  • MF: C16H18Cl2N4O
  • MW: 353.24600
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Beta-Amyloid(1-40)

β-Amyloid (1-40) is a primary protein in plaques found in the brains of patients with Alzheimer's disease.

  • CAS Number: 131438-79-4
  • MF: C194H295N53O58S
  • MW: 4329.867
  • Catalog: Peptides
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Gsk317354a

GSK317354A is a ROCK and GRK inhibitor. GSK317354A can be used for heart failure and Parkinson’s disease research[1].

  • CAS Number: 874119-13-8
  • MF: C25H18F4N6O
  • MW: 494.44
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LY3200882

LY3200882 is a novel and highly selective inhibitor of TGF-β receptor type 1 (TGFβRI).

  • CAS Number: 1898283-02-7
  • MF: C24H29N5O3
  • MW: 435.52
  • Catalog: TGF-β Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Rho Kinase Inhibitor III,Rockout

3-(4-Pyridyl)indole (Rockout) is a Rho-kinase (ROCK) inhibitor, with an IC50 of 25 μM. 3-(4-Pyridyl)indole can inhibit blebbing and cause dissolution of actin stress fibers in a wound healing assay[1].

  • CAS Number: 7272-84-6
  • MF: C13H10N2
  • MW: 194.23200
  • Catalog: ROCK
  • Density: 1.211g/cm3
  • Boiling Point: 406.7ºC at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 185.2ºC

TCS 21311

TCS 21311 (NIBR3049) is a potent, highly selective JAK3 inhibitor with an IC50 of 8 nM, it displays >100-fold selectivity over JAK1, JAK2 and TYK2. TCS 21311 (NIBR3049) inhibits PKCα, PKCθ, and GSK3β with IC50s of 13, 68, and 3 nM, respectively[1].

  • CAS Number: 1260181-14-3
  • MF: C27H25F3N4O4
  • MW: 526.50700
  • Catalog: JAK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Phosphate acceptor peptide

Phosphate acceptor peptide is a substrate for cAMP-dependent protein kinase (PKA). phosphate acceptor peptide is also a weak PKC inhibitor[1].

  • CAS Number: 93511-94-5
  • MF: C41H74N16O11
  • MW: 967.13
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

AR-13503

AR-13503 a ROCK/PKC inhibitor, inhibiting angiogenesis and enhancing retinal pigment epithelium (RPE) permeability. AR-13503 also inhibits the formation of aberrant neovascularization (NV) in oxygen-induced retinopathy (OIR) model in mice[1][2].

  • CAS Number: 1254032-16-0
  • MF: C19H19N3O2
  • MW: 321.37
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LDN 212854

LDN-212854 is a novel BMP inhibitor that exhibits substantially greater selectivity for BMP versus the TGF-β type I receptors; possesses a bias towards ALK2(IC50=1.3 nM) versus ALK1 and ALK3 compared to other inhibitors.IC50 value: 1.3 nM [1]Target: ALK2 In vitro, LDN-212854 exhibits some selectivity for ALK2 in preference to other BMP type I receptors, ALK1 and ALK3, which may permit the interrogation of ALK2-mediated signaling, transcriptional activity and function. LDN-212854 potently inhibitsheterotopic ossification in an inducible transgenic mutant ALK2 mouse model of fibrodysplasia ossificans progressiva.

  • CAS Number: 1432597-26-6
  • MF: C25H22N6
  • MW: 406.482
  • Catalog: TGF-β Receptor
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H-1152 (dihydrochloride)

H-1152 dihydrochloride is a membrane-permeable and selective ROCK inhibitor, with a Ki value of 1.6 nM, and an IC50 value of 12 nM for ROCK2.

  • CAS Number: 871543-07-6
  • MF: C16H23Cl2N3O2S
  • MW: 392.344
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

H7

PKC-IN-5 (compound H-7) is a potent PKC (protein kinase C) inhibitor. At 100 μM, PKC-IN-5 completely inhibits both TPA (skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate) and phospholipase C-induced ODC (ornithine decarboxylase)[1].

  • CAS Number: 108930-17-2
  • MF: C14H19Cl2N3O2S
  • MW: 364.291
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: 495.3ºC at 760mmHg
  • Melting Point: 215-225 °C
  • Flash Point: 253.3ºC

Mitoxantrone 2HCl

Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM.

  • CAS Number: 70476-82-3
  • MF: C22H30Cl2N4O6
  • MW: 517.403
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: 805.7ºC at 760 mmHg
  • Melting Point: 203-205ºC
  • Flash Point: 441.1ºC

ROCK-IN-1

ROCK-IN-1 is a potent inhibitor of ROCK, with an IC50 of 1.2 nM for ROCK2.

  • CAS Number: 934387-35-6
  • MF: C20H18FN3O
  • MW: 335.37
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

LDN-193189 HCl

LDN193189 Hydrochloride is a BMP signaling inhibitor, inhibiting ALK1, ALK2, ALK3 and ALK6 with IC50s of 0.8, 0.8, 5.3, 16.7 nM, respectively.

  • CAS Number: 1062368-62-0
  • MF: C25H26Cl4N6
  • MW: 552.33
  • Catalog: TGF-β Receptor
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Ruboxistaurin-d6 hydrochloride

Ruboxistaurin-d6 (LY333531-d6) hydrochloride is the deuterium labeled Ruboxistaurin hydrochloride. Ruboxistaurin (LY333531) hydrochloride is an orally active, selective PKC beta inhibitor (Ki=2 nM). Ruboxistaurin hydrochloride exhibits ATP dependent competitive inhibition of PKC beta I with an IC50 of 4.7 nM. Ruboxistaurin hydrochloride inhibits PKC beta II with an IC50 of 5.9 nM[1][2].

  • CAS Number: 1794767-04-6
  • MF: C28H23D6ClN4O3
  • MW: 511.04
  • Catalog: PKC
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

Bisindolylmaleimide I (GF109203X)

Bisindolylmaleimide I (GF109203X) is a highly selective, cell-permeable, and reversible protein kinase C (PKC) inhibitor with a Ki of 14 nM.

  • CAS Number: 133052-90-1
  • MF: C25H24N4O2
  • MW: 412.484
  • Catalog: PKC
  • Density: 1.3±0.1 g/cm3
  • Boiling Point: 685.6±55.0 °C at 760 mmHg
  • Melting Point: 208-210ºC
  • Flash Point: 368.5±31.5 °C

Daphnetin

Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative isolated from plants of the Genus Daphne, is a protein kinase inhibitor, with IC50s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively[1][2]. Daphnetin (7,8-dihydroxycoumarin) is a secondary metabolite of plants used in folk medicine to counter inflammatory and allergic diseases, also has been clinically used in the treatment of coagulation disorders, rheumatoid arthritis with anti-malarian and anti-pyretic properties[3].

  • CAS Number: 486-35-1
  • MF: C9H6O4
  • MW: 178.14
  • Catalog: PKC
  • Density: 1.6±0.1 g/cm3
  • Boiling Point: 430.4±45.0 °C at 760 mmHg
  • Melting Point: 265-268°C (dec.)
  • Flash Point: 184.5±22.2 °C

ROCK2-IN-2

ROCK2-IN-2 is a selective ROCK2 inhibitor extracted from patent US20180093978A1, Compound A-30, has an IC50 of <1 μM.

  • CAS Number: 1995065-79-6
  • MF: C18H12N6OS
  • MW: 360.39
  • Catalog: ROCK
  • Density: N/A
  • Boiling Point: N/A
  • Melting Point: N/A
  • Flash Point: N/A

SAR-407899

SAR407899 is a selective, potent and ATP-competitive ROCK inhibitor, with an IC50 of 135 nM for ROCK-2, and Kis of 36 nM and 41 nM for human and rat ROCK-2, respectively.

  • CAS Number: 923359-38-0
  • MF: C14H16N2O2
  • MW: 244.289
  • Catalog: ROCK
  • Density: 1.2±0.1 g/cm3
  • Boiling Point: 517.8±50.0 °C at 760 mmHg
  • Melting Point: N/A
  • Flash Point: 267.0±30.1 °C