NPASS Compound

Natural Product: NPC17834

Natural Product ID	NPC17834
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MLGUXXSGWWCJQW-KBPBESRZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	71296128
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000086] Pyrans [CHEMONTID:0000481] Pyranones and derivatives

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 30 32 0 0 0 0 0 0 0 0999 V2000 5.7009 -0.9459 -0.3284 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3607 -1.1074 0.0151 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3799 -0.1639 -0.1186 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0846 -0.4303 0.2534 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0641 0.5171 0.1268 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3104 0.1769 0.5424 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3302 0.0562 -0.4380 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7637 -0.0758 -0.1591 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5092 0.9549 0.4086 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8403 0.8028 0.6563 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5113 -0.3656 0.3615 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7968 -1.4004 -0.2006 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4495 -1.2406 -0.4491 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6346 -1.1778 0.0188 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4084 1.6773 -0.3672 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6339 1.9773 -0.7365 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9235 3.1198 -1.2124 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6842 1.0736 -0.6321 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0508 0.0222 0.1296 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3305 -1.7275 0.1144 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8686 -0.8579 -1.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7986 -1.3852 0.6605 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5344 0.2511 1.6202 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0999 0.2764 -1.5094 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9909 1.8736 0.6425 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4253 1.6112 1.1016 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5863 -0.4552 0.5743 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2824 -2.3251 -0.4444 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9180 -2.0864 -0.8964 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6946 1.3544 -0.9487 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 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 7 14 1 0 5 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 3 2 0 14 6 1 0 13 8 1 0 1 19 1 0 1 20 1 0 1 21 1 0 4 22 1 0 6 23 1 1 7 24 1 6 9 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 13 29 1 0 18 30 1 0 M END

Standard InCHIKey	MLGUXXSGWWCJQW-KBPBESRZSA-N
Standard InCHI	InChI=1S/C14H12O4/c1-16-10-7-11(17-12(15)8-10)14-13(18-14)9-5-3-2-4-6-9/h2-8,13-14H,1H3/t13-,14-/m0/s1
SMILES	COc1cc([C@H]2[C@H](c3ccccc3)O2)oc(=O)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	244.07	Volume:	244.373 ? Van der Waals volume.
Dense:	0.999	LogP:	2.495 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.755 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.631 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	16.0
TPSA:	51.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.778	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.136	Fsp³:	0.214
MCE-18:	48.529 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.431	Fluc inhibitor:	0.316 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.208 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.334 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.747	Promiscuous compounds:	0.345

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.781	MDCK Permeability:	-4.372
Pgp-inhibitor:	0.843	Pgp-substrate:	0.011
PAMPA:	0.021 ? 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):	0.001
20% Bioavailability (F20%):	0.012	30% Bioavailability (F30%):	0.143
50% Bioavailability (F50%):	0.186

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.371	MRP1:	0.838
Plasma Protein Binding (PPB):	93.209%	Volume Distribution (VD):	0.171
Fu:	7.021% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.084
BSEP inhibitor:	0.987

ADMET: Metabolism

CYP1A2-inhibitor:	0.024	CYP1A2-substrate:	0.664
CYP2C19-inhibitor:	0.874	CYP2C19-substrate:	0.621
CYP2C9-inhibitor:	0.375	CYP2C9-substrate:	0.125
CYP2D6-inhibitor:	0.019	CYP2D6-substrate:	0.315
CYP3A4-inhibitor:	0.56	CYP3A4-substrate:	0.291
CYP2B6-substrate:	0.008	CYP2C8-inhibitor:	0.35
HLM stability:	0.443 ? 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):

5.95

Half-life (T1/2):

1.792

ADMET: Toxicity

hERG Blockers:	0.127	hERG Blockers (10um):	0.408
Human Hepatotoxicity (H-HT):	0.732	Drug-induced Liver Injury (DILI):	0.745
AMES Toxicity:	0.721	Rat Oral Acute Toxicity:	0.504
Maximum Recommended Daily Dose:	0.552	Skin Sensitization:	0.847
Carcinogencity:	0.574	Eye Corrosion:	0.662
Eye Irritation:	0.99	Respiratory Toxicity:	0.407
Drug-induced Neurotoxicity:	0.914	Ototoxicity:	0.238
Hematotoxicity:	0.375	Drug-induced Nephrotoxicity:	0.365
Genotoxicity:	0.774	RPMI-8226 Immunitoxicity:	0.092
A549 Cytotoxicity:	0.115	Hek293 Cytotoxicity:	0.294
BCF:	1.433 ? 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:	3.868 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.967 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.58 ? 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
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	bud covers	n.a.	n.a.	PMID[11975520]
NPO18596	Melia dubia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12502333]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[12662107]
NPO19082	Creolophus cirrhatus	Species	Hericiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18596	Melia dubia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19008	Mentha cablin	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18529	Salvia broussoneti	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18596	Melia dubia	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19082	Creolophus cirrhatus	Species	Hericiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20691	Echinocereus merkeri	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8171	Artocarpus altilis	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18259	Chaetanthera chilensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18762	Ilex microdonta	Species	Aquifoliaceae	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 NPC17834 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	28841
0.1-0.2	19955
0.2-0.3	1035
0.3-0.4	24
0.4-0.5	3
0.5-0.6	1
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	Natural Product ID
0.5455	Remote Similarity	NPC270093

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC17834 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3765
0.1-0.2	5236
0.2-0.3	149
0.3-0.4	0
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