NPASS Compound

Natural Product: NPC20354

Natural Product ID	NPC20354
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OVDFVZLTXMMPDE-ZDUSSCGKSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	15489634
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002596] 4'-O-methylated flavonoids

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 36 38 0 0 0 0 0 0 0 0999 V2000 6.3668 -0.2542 -0.8366 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4429 -1.2169 -0.3683 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1167 -0.8550 -0.2205 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6982 0.4260 -0.5248 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3691 0.7858 -0.3758 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4154 -0.1028 0.0760 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8372 -1.3646 0.3738 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1528 -1.7425 0.2329 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0262 0.3254 0.2160 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3661 0.5992 1.6583 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7063 1.2309 1.6206 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9636 2.2214 2.3447 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7142 0.6752 0.7249 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0451 1.0447 0.8158 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9389 0.4780 -0.0636 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5405 -0.4353 -1.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2052 -0.7736 -1.0707 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2494 -0.2411 -0.2153 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9086 -0.6050 -0.2971 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7592 -1.6940 -2.0204 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4586 -1.0086 -1.9099 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4328 1.9651 1.7800 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3796 -0.6671 -0.9646 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4010 0.6033 -0.1032 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0244 0.2194 -1.7922 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4402 1.1339 -0.8812 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1081 1.8018 -0.6308 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0746 -2.0668 0.7325 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4722 -2.7498 0.4740 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1354 1.2922 -0.3256 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4016 1.3132 2.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3505 -0.3256 2.2702 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0061 0.7443 -0.0253 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2883 -2.5786 -2.0414 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4068 -1.1419 -1.5868 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2515 2.9636 1.6362 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 17 20 1 0 16 21 1 0 14 22 1 0 8 3 1 0 19 9 1 0 18 13 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 5 27 1 0 7 28 1 0 8 29 1 0 9 30 1 6 10 31 1 0 10 32 1 0 15 33 1 0 20 34 1 0 21 35 1 0 22 36 1 0 M END

Standard InCHIKey	OVDFVZLTXMMPDE-ZDUSSCGKSA-N
Standard InCHI	InChI=1S/C16H14O6/c1-21-9-4-2-8(3-5-9)13-7-11(18)14-10(17)6-12(19)15(20)16(14)22-13/h2-6,13,17,19-20H,7H2,1H3/t13-/m0/s1
SMILES	COc1ccc(cc1)[C@@H]1CC(=O)c2c(cc(c(c2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	302.08	Volume:	293.909 ? Van der Waals volume.
Dense:	1.028	LogP:	2.736 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.888 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.104 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	96.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.582	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.91	Fsp³:	0.188
MCE-18:	57.789 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.664	Fluc inhibitor:	0.699 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.308 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.281 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.392	Promiscuous compounds:	0.116

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.159	MDCK Permeability:	-4.818
Pgp-inhibitor:	0.499	Pgp-substrate:	0.013
PAMPA:	0.14 ? 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):	0.017
20% Bioavailability (F20%):	0.067	30% Bioavailability (F30%):	0.834
50% Bioavailability (F50%):	0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.889
Plasma Protein Binding (PPB):	97.676%	Volume Distribution (VD):	-0.363
Fu:	1.908% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.795
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.976
BSEP inhibitor:	0.379

ADMET: Metabolism

CYP1A2-inhibitor:	0.942	CYP1A2-substrate:	0.609
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.964
CYP2C9-inhibitor:	0.149	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.209	CYP2D6-substrate:	0.23
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.831
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.944
HLM stability:	0.963 ? 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):

11.401

Half-life (T1/2):

1.421

ADMET: Toxicity

hERG Blockers:	0.108	hERG Blockers (10um):	0.511
Human Hepatotoxicity (H-HT):	0.723	Drug-induced Liver Injury (DILI):	0.848
AMES Toxicity:	0.792	Rat Oral Acute Toxicity:	0.655
Maximum Recommended Daily Dose:	0.666	Skin Sensitization:	0.921
Carcinogencity:	0.389	Eye Corrosion:	0.06
Eye Irritation:	0.986	Respiratory Toxicity:	0.931
Drug-induced Neurotoxicity:	0.45	Ototoxicity:	0.534
Hematotoxicity:	0.235	Drug-induced Nephrotoxicity:	0.65
Genotoxicity:	0.93	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.872	Hek293 Cytotoxicity:	0.42
BCF:	1.367 ? 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:	3.988 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.167 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.604 ? 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
NPO40096	Dasymaschalon dasymaschalum	Species	Annonaceae	Eukaryota	Twigs	n.a.	n.a.	PMID[31661271]
NPO40096	Dasymaschalon dasymaschalum	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
IC50	1

Activity Type	# Activity
Others	1

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.	IC50	=	256500.0	nM	PMID[31661271]

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 NPC20354 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	25146
0.1-0.2	20313
0.2-0.3	3797
0.3-0.4	459
0.4-0.5	114
0.5-0.6	22
0.6-0.7	4
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
0.6667	Remote Similarity	NPC274784
0.6667	Remote Similarity	NPC20709
0.6275	Remote Similarity	NPC6407
0.6275	Remote Similarity	NPC545184
0.5849	Remote Similarity	NPC162869
0.5818	Remote Similarity	NPC469758
0.5763	Remote Similarity	NPC148757
0.5741	Remote Similarity	NPC296917
0.5741	Remote Similarity	NPC170907
0.5472	Remote Similarity	NPC188243
0.5472	Remote Similarity	NPC110228
0.5455	Remote Similarity	NPC156057
0.5273	Remote Similarity	NPC150648
0.5185	Remote Similarity	NPC213322
0.5179	Remote Similarity	NPC329203
0.5179	Remote Similarity	NPC222342
0.5172	Remote Similarity	NPC302950
0.5091	Remote Similarity	NPC32441
0.5091	Remote Similarity	NPC243083
0.5091	Remote Similarity	NPC13768
0.5091	Remote Similarity	NPC482121
0.5091	Remote Similarity	NPC287246
0.5091	Remote Similarity	NPC482487
0.5091	Remote Similarity	NPC79943
0.5091	Remote Similarity	NPC270964
0.5091	Remote Similarity	NPC603284

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC20354 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4304
0.1-0.2	4690
0.2-0.3	145
0.3-0.4	6
0.4-0.5	2
0.5-0.6	3
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
0.5172	Remote Similarity	NPD1934	Phase 0
0.5091	Remote Similarity	NPD1550	Phase 2
0.5091	Remote Similarity	NPD1552	Clinical (unspecified phase)

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