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[58] [59] 5E1, a monoclonal antibody against Shh, has been shown to inhibit medulloblastoma growth in mouse models. [60] 5E1 also restricts the proliferation of pancreatic cancer cells in mice. [61] While shown to be effective in the lab, both these Shh inhibitors are yet to make their way to human trials.
The SHH gene is a member of the hedgehog gene family with five variations of DNA sequence alterations or splice variants. [37] SHH is located on chromosome seven and initiates the production of Sonic Hedgehog protein. [37] This protein sends short- and long-range signals to embryonic tissues to regulate development. [38]
Silmitasertib is in clinical trials for use as an adjunct to chemotherapy in the treatment of cholangiocarcinoma (bile duct cancer), [1] is in phase I and II clinical trials for the treatment of recurrent Sonic Hedgehog (SHH) medulloblastoma, [2] [3] and in preclinical development for other cancers, including hematological and lymphoid ...
It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA). [8] Smoothened (Smo) is a key transmembrane protein that is a key component of the hedgehog signaling pathway, a cell-cell communication system critical for embryonic development and adult tissue homeostasis.
Holoprosencephaly, the failure of the embryonic prosencephalon to divide to form cerebral hemispheres, occurs with a frequency of about 1 in 8,000 live births and about 1 in 200 spontaneous abortions in humans and is commonly linked to mutations in genes involved in the hedgehog pathway, including SHH and PTCH. [37]
Noggin, a known inhibitor of BMP4, is found within the matrix cells of the hair bulb. Other important factors to consider in the development of hair is the expression of Shh (sonic hedgehog), BMP7, BMP2, WNT, and β-catenin as these are required in early stage morphogenesis. [40]
2735 14632 Ensembl ENSG00000111087 ENSMUSG00000025407 UniProt P08151 P47806 RefSeq (mRNA) NM_001160045 NM_001167609 NM_005269 NM_010296 RefSeq (protein) NP_001153517 NP_001161081 NP_005260 NP_034426 Location (UCSC) Chr 12: 57.46 – 57.47 Mb Chr 10: 127.17 – 127.18 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Zinc finger protein GLI1 also known as glioma-associated oncogene is a ...
PTEN inhibitors, such as bisperoxovanadium, [35] can enhance the PI3K/AKT pathway to promote cell migration, [36] survival [37] and proliferation. [7] While there are some concerns over possible cell cycle dysregulation and tumorigenesis, temporary and moderate PTEN inhibition may confer neuroprotection against traumatic brain injury [ 38 ] and ...