NPASS Compound

Natural Product: NPC471457

Natural Product ID	NPC471457
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isoscutellarein 5-O-Beta-D-Glucopyranoside
IUPAC Name	7,8-dihydroxy-2-(4-hydroxyphenyl)-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL250694
PubChem CID	5320057
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 54 57 0 0 0 0 0 0 0 0999 V2000 2.4176 -0.2801 -1.5588 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4774 0.3695 -0.6982 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2525 0.0713 0.6864 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9880 0.1143 1.2426 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7993 0.1242 2.6035 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5184 0.1677 3.0857 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5843 0.2016 2.2285 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4247 0.1926 0.8687 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8990 0.1478 0.4110 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0992 0.1374 -1.0238 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1444 0.4846 -1.7818 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4501 0.2239 -0.0212 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7930 0.2693 0.2981 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4306 1.5841 -0.1514 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8245 1.5866 0.4727 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5580 0.4615 -0.1936 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8398 -0.8255 0.1601 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5135 -0.8225 -0.1503 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6121 -1.9797 -0.3857 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5899 -2.0679 -1.7655 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8975 0.4053 0.1003 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4459 2.8135 0.3243 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5215 1.5272 -1.5399 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3365 0.1774 4.4735 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9041 0.0902 3.4592 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8291 -0.1413 -1.0139 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2783 -1.3783 -0.6098 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5384 -1.8391 -0.9114 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3810 -1.0445 -1.6390 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9841 0.2041 -2.0703 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7022 0.6316 -1.7438 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6561 -1.4930 -1.9527 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5271 -1.3621 -1.6504 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5064 0.1570 -2.5700 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3916 1.4559 -0.8113 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5469 0.2345 2.7066 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9171 0.2776 1.3918 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8963 2.4502 0.2295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7376 1.3362 1.5479 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4416 0.6022 -1.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9094 -0.8941 1.2764 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2369 -2.9579 0.0041 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6691 -1.8968 -0.0778 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3062 -1.2627 -2.2268 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4485 0.9815 -0.5074 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9204 3.3450 -0.3465 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4451 0.5759 -1.8695 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0503 -0.7070 4.8956 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2118 0.8988 3.9565 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6024 -1.9891 -0.0388 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8652 -2.8019 -0.5874 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6779 0.8003 -2.6417 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4286 1.6166 -2.1004 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4934 -0.9742 -1.7344 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 8 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 16 21 1 0 15 22 1 0 14 23 1 0 6 24 1 0 5 25 1 0 2 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 29 32 1 0 10 1 1 0 9 4 1 0 18 13 1 0 31 26 1 0 1 33 1 0 1 34 1 0 2 35 1 0 7 36 1 0 13 37 1 0 14 38 1 0 15 39 1 0 16 40 1 0 17 41 1 0 19 42 1 0 19 43 1 0 20 44 1 0 21 45 1 0 22 46 1 0 23 47 1 0 24 48 1 0 25 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 M END

Standard InCHIKey	YYSRTHIUABRSAB-UZWZRHDMSA-N
Standard InCHI	InChI=1S/C21H22O11/c22-7-14-17(27)18(28)19(29)21(32-14)31-13-6-11(25)16(26)20-15(13)10(24)5-12(30-20)8-1-3-9(23)4-2-8/h1-4,6,12,14,17-19,21-23,25-29H,5,7H2/t12?,14-,17-,18+,19-,21-/m1/s1
SMILES	C1C(OC2=C(C(=CC(=C2C1=O)OC3C(C(C(C(O3)CO)O)O)O)O)O)C4=CC=C(C=C4)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.12	Volume:	415.784 ? Van der Waals volume.
Dense:	1.083	LogP:	-0.527 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.375 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.815 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.303	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.175	Fsp³:	0.381
MCE-18:	90.552 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.318	Fluc inhibitor:	0.135 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.203 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.64 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.271	Promiscuous compounds:	0.144

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.431	MDCK Permeability:	-5.006
Pgp-inhibitor:	0.0	Pgp-substrate:	0.23
PAMPA:	0.999 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.805
20% Bioavailability (F20%):	0.675	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.977
Plasma Protein Binding (PPB):	78.552%	Volume Distribution (VD):	-0.144
Fu:	22.098% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.001
OATP1B3 inhibitor:	0.944	BCRP inhibitor:	0.985
BSEP inhibitor:	0.026

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.591	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.073	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.012
HLM stability:	0.02 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

3.395

Half-life (T1/2):

2.833

ADMET: Toxicity

hERG Blockers:	0.088	hERG Blockers (10um):	0.459
Human Hepatotoxicity (H-HT):	0.719	Drug-induced Liver Injury (DILI):	0.449
AMES Toxicity:	0.705	Rat Oral Acute Toxicity:	0.313
Maximum Recommended Daily Dose:	0.283	Skin Sensitization:	0.7
Carcinogencity:	0.365	Eye Corrosion:	0.0
Eye Irritation:	0.218	Respiratory Toxicity:	0.032
Drug-induced Neurotoxicity:	0.101	Ototoxicity:	0.963
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.164
Genotoxicity:	0.633	RPMI-8226 Immunitoxicity:	0.042
A549 Cytotoxicity:	0.383	Hek293 Cytotoxicity:	0.68
BCF:	0.381 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.841 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.53 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.659 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO2284	Cephalotaxus koreana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16574412]
NPO2284	Cephalotaxus koreana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17994703]
NPO2284	Cephalotaxus koreana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2284	Cephalotaxus koreana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Inhibition	2

Activity Type	# Activity
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Inhibition	=	63.0	%	PMID[15267241]
NPT2	Others	Unspecified	n.a.	Inhibition	=	86.0	%	PMID[15911319]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC471457 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	15866
0.1-0.2	28287
0.2-0.3	4434
0.3-0.4	990
0.4-0.5	234
0.5-0.6	31
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8182	Intermediate Similarity	NPC169248
0.8182	Intermediate Similarity	NPC72649
0.7324	Intermediate Similarity	NPC206378
0.6944	Remote Similarity	NPC39351
0.6575	Remote Similarity	NPC170475
0.6447	Remote Similarity	NPC5778
0.6316	Remote Similarity	NPC181014
0.6282	Remote Similarity	NPC479540
0.6104	Remote Similarity	NPC29830
0.6053	Remote Similarity	NPC26195
0.6047	Remote Similarity	NPC168789
0.5921	Remote Similarity	NPC97052
0.5921	Remote Similarity	NPC45400
0.5844	Remote Similarity	NPC219163
0.5765	Remote Similarity	NPC472876
0.5679	Remote Similarity	NPC236934
0.5474	Remote Similarity	NPC483821
0.5455	Remote Similarity	NPC601828
0.5325	Remote Similarity	NPC99233
0.5316	Remote Similarity	NPC328093
0.5316	Remote Similarity	NPC259182
0.5316	Remote Similarity	NPC163191
0.5312	Remote Similarity	NPC321916
0.5263	Remote Similarity	NPC121001
0.5238	Remote Similarity	NPC259834
0.5185	Remote Similarity	NPC225445
0.5185	Remote Similarity	NPC106625
0.5181	Remote Similarity	NPC472381
0.5152	Remote Similarity	NPC483820
0.5125	Remote Similarity	NPC308265
0.5125	Remote Similarity	NPC88484
0.5114	Remote Similarity	NPC271270
0.5077	Remote Similarity	NPC142319
0.5067	Remote Similarity	NPC199335
0.5067	Remote Similarity	NPC477240
0.5063	Remote Similarity	NPC165720
0.5063	Remote Similarity	NPC148273
0.506	Remote Similarity	NPC472320
0.5056	Remote Similarity	NPC142860
0.5056	Remote Similarity	NPC152538
0.5056	Remote Similarity	NPC246469
0.5056	Remote Similarity	NPC89088

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC471457 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4033
0.1-0.2	4982
0.2-0.3	113
0.3-0.4	18
0.4-0.5	4
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data