condition found tbRes List
SK, Shikonin: Click to Expand ⟱
Features:
The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin.
Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon).
Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao'
-Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties
-Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin
-ic50 cancer cells 1-10uM, normal cells >10uM

-known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway)

Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg
Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin)

-Note half-life15-30mins or 8hr?.
BioAv low, poor water solubility
Pathways:
- usually induce ROS production in cancer cells, and reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


FAK, FAK signaling: Click to Expand ⟱
Source: HalifaxProj(inhibit)
Type:
FAK (Focal Adhesion Kinase) is a non-receptor tyrosine kinase that plays a crucial role in cellular processes such as adhesion, migration, proliferation, and survival. It is primarily localized at focal adhesions, where it interacts with integrins and other signaling molecules. FAK promotes cell proliferation by activating signaling pathways such as the PI3K/Akt and MAPK/ERK pathways. These pathways are often upregulated in cancer cells, leading to uncontrolled growth.
Scientific Papers found: Click to Expand⟱
2355- SK,    Pharmacological properties and derivatives of shikonin-A review in recent years
- Review, Var, NA
AntiCan↑, anticancer effects on various types of cancer by inhibiting cell proliferation and migration, inducing apoptosis, autophagy, and necroptosis.
TumCP↓,
TumCMig↓,
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
ROS↑, Shikonin also triggers Reactive Oxygen Species (ROS) generation
TrxR1↓, inhibiting the activation of TrxR1, PKM2, RIP1/3, Src, and FAK
PKM2↓,
RIP1↓,
RIP3↓,
Src↓,
FAK↓,
PI3K↓, modulating the PI3K/AKT/mTOR and MAPKs signaling;
Akt↓, shikonin induced a dose-dependent reduction of miR-19a to inhibit the activity of PI3K/AKT/mTOR pathway
mTOR↓,
GRP58↓, shikonin induced apoptosis in human myeloid cell line HL-60 cells through downregulating the expression of ERS protein ERP57 (42).
MMPs↓, hikonin suppressed cell migration through inhibiting the NF-κB pathway and reducing the expression of MMP-2 and MMP-9
ATF2↓, shikonin inhibited cell proliferation and tumor growth through suppressing the ATF2 pathway
cl‑PARP↑, shikonin significantly upregulated the expression of apoptosis-related proteins cleaved PARP and caspase-3 and increased cell apoptosis through increasing the phosphorylation of p38 MAPK and JNK, and inhibiting the phosphorylation of ERK
Casp3↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↓,

2197- SK,    Shikonin derivatives for cancer prevention and therapy
- Review, Var, NA
ROS↑, This compound accumulates in the mitochondria, which leads to the generation of reactive oxygen species (ROS), and deregulates intracellular Ca2+ levels.
Ca+2↑,
BAX↑, shikonin alone by increasing the expression of the pro-apoptotic Bax protein and decreasing the expression of the anti-apoptotic Bcl2 protein
Bcl-2↓,
MMP9↓, This treatment also inhibited metastasis by decreasing the expression of MMP-9 and NF-kB p65 without affecting MMP-2 expression.
NF-kB↓,
PKM2↓, Figure 4
Hif1a↓,
NRF2↓,
P53↑,
DNMT1↓,
MDR1↓,
COX2↓,
VEGF↓,
EMT↓,
MMP7↓,
MMP13↓,
uPA↓,
RIP1↑,
RIP3↑,
Casp3↑,
Casp7↑,
Casp9↑,
P21↓,
DFF45↓,
TRAIL↑,
PTEN↑,
mTOR↓,
AR↓,
FAK↓,
Src↓,
Myc↓,
RadioS↑, shikonin acted as a radiosensitizer because of the high ROS production it induced.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   AntiCan↑,1,   Apoptosis↑,1,   AR↓,1,   ATF2↓,1,   BAX↑,1,   Bcl-2↓,1,   Ca+2↑,1,   Casp3↑,2,   Casp7↑,1,   Casp9↑,1,   COX2↓,1,   DFF45↓,1,   DNMT1↓,1,   EMT↓,1,   p‑ERK↓,1,   FAK↓,2,   GRP58↓,1,   Hif1a↓,1,   p‑JNK↑,1,   MDR1↓,1,   MMP13↓,1,   MMP7↓,1,   MMP9↓,1,   MMPs↓,1,   mTOR↓,2,   Myc↓,1,   Necroptosis↑,1,   NF-kB↓,1,   NRF2↓,1,   P21↓,1,   p‑p38↑,1,   P53↑,1,   cl‑PARP↑,1,   PI3K↓,1,   PKM2↓,2,   PTEN↑,1,   RadioS↑,1,   RIP1↓,1,   RIP1↑,1,   RIP3↓,1,   RIP3↑,1,   ROS↑,2,   Src↓,2,   TRAIL↑,1,   TrxR1↓,1,   TumAuto↑,1,   TumCMig↓,1,   TumCP↓,1,   uPA↓,1,   VEGF↓,1,  
Total Targets: 51

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: FAK, FAK signaling
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:110  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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