NPASS Compound

Natural Product: NPC271899

Natural Product ID	NPC271899
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UVYUUQGGBNKRFU-ZDUSSCGKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12414274
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000119] Acetophenones

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 29 30 0 0 0 0 0 0 0 0999 V2000 -3.7172 -1.3819 1.2077 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3848 -0.3932 0.4074 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4318 0.6122 0.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0276 -0.2445 -0.1283 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0178 -1.2430 0.3694 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2500 -0.4405 0.2058 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5539 -0.8970 0.1009 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5653 0.0075 -0.0428 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2493 1.3380 -0.0776 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9569 1.8020 0.0258 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0795 0.8950 0.1720 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4496 0.9996 0.3008 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9602 -0.4254 -0.1578 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2157 -1.6666 -0.1214 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0624 0.5408 -0.3133 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0213 -2.1150 1.5121 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7382 -1.4993 1.6038 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3995 0.0738 0.0111 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2138 0.9462 -1.0252 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4259 1.4890 0.6923 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0923 -0.2465 -1.2428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0010 -2.1624 -0.2256 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2053 -1.4082 1.4566 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7960 -1.9620 0.1298 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0232 2.0987 -0.1909 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6931 2.8466 -0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7580 1.2572 -1.1311 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9911 0.0186 -0.5564 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1305 1.1606 0.6014 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 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 11 12 1 0 8 13 1 0 13 14 2 0 13 15 1 0 12 4 1 0 11 6 1 0 1 16 1 0 1 17 1 0 3 18 1 0 3 19 1 0 3 20 1 0 4 21 1 6 5 22 1 0 5 23 1 0 7 24 1 0 9 25 1 0 10 26 1 0 15 27 1 0 15 28 1 0 15 29 1 0 M END

Standard InCHIKey	UVYUUQGGBNKRFU-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C13H14O2/c1-8(2)13-7-11-6-10(9(3)14)4-5-12(11)15-13/h4-6,13H,1,7H2,2-3H3/t13-/m0/s1
SMILES	C=C(C)[C@@H]1Cc2cc(ccc2O1)C(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	202.1	Volume:	220.69 ? Van der Waals volume.
Dense:	0.916	LogP:	3.281 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.08 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.256 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	12.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.544	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.715	Fsp³:	0.308
MCE-18:	38.824 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.194	Fluc inhibitor:	0.206 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.061 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.057 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.884	Promiscuous compounds:	0.238

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.56	MDCK Permeability:	-4.593
Pgp-inhibitor:	0.621	Pgp-substrate:	0.113
PAMPA:	0.036 ? 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):	0.002
20% Bioavailability (F20%):	0.054	30% Bioavailability (F30%):	0.09
50% Bioavailability (F50%):	0.481

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.575	MRP1:	0.856
Plasma Protein Binding (PPB):	95.741%	Volume Distribution (VD):	0.074
Fu:	3.779% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.171
OATP1B3 inhibitor:	0.808	BCRP inhibitor:	0.2
BSEP inhibitor:	0.931

ADMET: Metabolism

CYP1A2-inhibitor:	0.2	CYP1A2-substrate:	0.919
CYP2C19-inhibitor:	0.144	CYP2C19-substrate:	0.351
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.065
CYP2D6-inhibitor:	0.019	CYP2D6-substrate:	0.13
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.689
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.385 ? 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):

9.347

Half-life (T1/2):

0.985

ADMET: Toxicity

hERG Blockers:	0.206	hERG Blockers (10um):	0.444
Human Hepatotoxicity (H-HT):	0.636	Drug-induced Liver Injury (DILI):	0.628
AMES Toxicity:	0.82	Rat Oral Acute Toxicity:	0.636
Maximum Recommended Daily Dose:	0.791	Skin Sensitization:	0.773
Carcinogencity:	0.706	Eye Corrosion:	0.256
Eye Irritation:	0.984	Respiratory Toxicity:	0.896
Drug-induced Neurotoxicity:	0.834	Ototoxicity:	0.391
Hematotoxicity:	0.428	Drug-induced Nephrotoxicity:	0.486
Genotoxicity:	0.89	RPMI-8226 Immunitoxicity:	0.078
A549 Cytotoxicity:	0.17	Hek293 Cytotoxicity:	0.237
BCF:	0.924 ? 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:	3.549 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.224 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.596 ? 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
NPO25179	Guilandina bonduc	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26756595]
NPO12556	Fritillaria verticillata	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2545	Aster scaber	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16880	Lupinus texensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2545	Aster scaber	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12556	Fritillaria verticillata	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12556	Fritillaria verticillata	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2545	Aster scaber	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12556	Fritillaria verticillata	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3771	Sphaeria sassafras	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO5035	Schistostephium heptalobum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16880	Lupinus texensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16791	Ligularia virgaurea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25179	Guilandina bonduc	Species	Fabaceae	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

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

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 NPC271899 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	21213
0.1-0.2	27189
0.2-0.3	1389
0.3-0.4	45
0.4-0.5	5
0.5-0.6	5
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC11799
1.0	High Similarity	NPC141252
0.7692	Intermediate Similarity	NPC939
0.6977	Remote Similarity	NPC170546
0.6977	Remote Similarity	NPC66246
0.6842	Remote Similarity	NPC265634
0.6667	Remote Similarity	NPC183348
0.6579	Remote Similarity	NPC470858
0.6522	Remote Similarity	NPC470976
0.65	Remote Similarity	NPC65539
0.6327	Remote Similarity	NPC196979
0.625	Remote Similarity	NPC247743
0.6122	Remote Similarity	NPC470977
0.5952	Remote Similarity	NPC470859
0.5882	Remote Similarity	NPC282230
0.5455	Remote Similarity	NPC137009
0.5333	Remote Similarity	NPC470856
0.5263	Remote Similarity	NPC15083

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC271899 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3234
0.1-0.2	5764
0.2-0.3	151
0.3-0.4	1
0.4-0.5	0
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