NPASS Compound

Natural Product: NPC273548

Natural Product ID	NPC273548
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QOFDITUHNAYYJC-RYUDHWBXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12444385
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000145] Coumarins and derivatives [CHEMONTID:0003484] Pyranocoumarins [CHEMONTID:0003485] Angular pyranocoumarins

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 51 54 0 0 0 0 0 0 0 0999 V2000 -3.7875 0.3795 -3.8179 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1215 -0.2692 -2.4962 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0137 -0.1117 -1.4600 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7482 -0.7400 -1.8600 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5369 -1.4691 -2.9980 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3145 -2.0278 -3.3084 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1808 -2.6983 -4.3894 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6940 -1.8631 -2.4907 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5469 -1.1640 -1.3679 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6703 -1.0597 -0.5891 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9514 -1.6581 -0.9380 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0113 -1.5438 -0.1768 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9901 -0.8030 1.0878 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3640 -1.7767 2.2276 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0941 0.2627 1.0466 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7615 -0.2542 1.3810 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6487 -0.3629 0.6004 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4419 0.2135 0.9512 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3213 0.9652 2.1864 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2091 0.8400 3.0620 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8060 1.8721 2.4527 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3459 3.2715 2.0622 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0525 1.4974 1.6991 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0290 0.8015 2.6164 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8295 0.7029 0.5871 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6819 0.1060 0.1666 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6586 -0.5905 -1.0236 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9638 -0.2634 -4.6993 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7282 0.6876 -3.8193 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3925 1.3241 -3.9488 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0505 0.2268 -2.1230 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4102 -1.3346 -2.6143 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9295 0.9999 -1.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3953 -0.6003 -0.5489 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3276 -1.6351 -3.6820 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0471 -2.2316 -1.8747 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9582 -2.0332 -0.5137 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7230 -1.5860 3.0980 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2271 -2.8136 1.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4101 -1.5961 2.5558 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2887 0.6453 2.0564 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8591 1.0253 0.3062 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0028 -0.2722 0.7007 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0056 1.8678 3.5422 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2344 3.2721 0.9543 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6660 3.4393 2.5128 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0280 4.0645 2.3965 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5372 2.4405 1.3753 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7467 1.5183 3.0476 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5836 0.0006 2.1022 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4470 0.3339 3.4322 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 6 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 1 0 13 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 26 27 2 0 27 4 1 0 27 9 1 0 17 10 1 0 26 18 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 0 2 32 1 0 3 33 1 0 3 34 1 0 5 35 1 0 11 36 1 0 12 37 1 0 14 38 1 0 14 39 1 0 14 40 1 0 15 41 1 0 15 42 1 0 15 43 1 0 21 44 1 1 22 45 1 0 22 46 1 0 22 47 1 0 23 48 1 6 24 49 1 0 24 50 1 0 24 51 1 0 M END

Standard InCHIKey	QOFDITUHNAYYJC-RYUDHWBXSA-N
Standard InCHI	InChI=1S/C22H24O5/c1-6-7-13-10-15(23)26-19-14-8-9-22(4,5)27-20(14)17-18(24)11(2)12(3)25-21(17)16(13)19/h8-12H,6-7H2,1-5H3/t11-,12-/m0/s1
SMILES	CCCc1cc(=O)oc2c3C=CC(C)(C)Oc3c3C(=O)[C@@H](C)[C@H](C)Oc3c12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.16	Volume:	380.338 ? Van der Waals volume.
Dense:	0.968	LogP:	4.57 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.821 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.471 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	23.0
TPSA:	65.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.729	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.039	Fsp³:	0.455
MCE-18:	82.875 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.544	Fluc inhibitor:	0.012 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.836 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.716 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.278	Promiscuous compounds:	0.052

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.63	MDCK Permeability:	-4.598
Pgp-inhibitor:	0.785	Pgp-substrate:	0.005
PAMPA:	0.443 ? 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):	0.0
20% Bioavailability (F20%):	0.667	30% Bioavailability (F30%):	0.663
50% Bioavailability (F50%):	0.928

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.051	MRP1:	0.993
Plasma Protein Binding (PPB):	98.78%	Volume Distribution (VD):	0.08
Fu:	1.043% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.941	BCRP inhibitor:	0.013
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.395	CYP1A2-substrate:	0.938
CYP2C19-inhibitor:	0.998	CYP2C19-substrate:	0.528
CYP2C9-inhibitor:	0.181	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.008	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.879
HLM stability:	0.955 ? 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):

4.746

Half-life (T1/2):

1.101

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.414
Human Hepatotoxicity (H-HT):	0.68	Drug-induced Liver Injury (DILI):	0.885
AMES Toxicity:	0.473	Rat Oral Acute Toxicity:	0.518
Maximum Recommended Daily Dose:	0.556	Skin Sensitization:	0.866
Carcinogencity:	0.712	Eye Corrosion:	0.066
Eye Irritation:	0.875	Respiratory Toxicity:	0.758
Drug-induced Neurotoxicity:	0.175	Ototoxicity:	0.312
Hematotoxicity:	0.587	Drug-induced Nephrotoxicity:	0.461
Genotoxicity:	0.659	RPMI-8226 Immunitoxicity:	0.165
A549 Cytotoxicity:	0.162	Hek293 Cytotoxicity:	0.478
BCF:	2.134 ? 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:	4.495 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.599 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.045 ? 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
NPO22503	Salix matsudana	Species	Salicaceae	Eukaryota	n.a.	leaf	n.a.	PMID[18794770]
NPO20091	Iotrochota baculifera	Species	Iotrochotidae	Eukaryota	Chinese	n.a.	n.a.	PMID[20624681]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7288442]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7400820]
NPO20091	Iotrochota baculifera	Species	Iotrochotidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21601	Crocus sieberi	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20897	Suberites domuncula	Species	Suberitidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20382	Ramalina paludosa	Species	Ramalinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20091	Iotrochota baculifera	Species	Iotrochotidae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27363	Gynochthodes officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27363	Gynochthodes officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22503	Salix matsudana	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21601	Crocus sieberi	Species	Iridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21034	Nocardia alba	Species	Nocardiaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO21852	Montanoa karwinskii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20773	Jacobaea persoonii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20458	Strychnos decussata	Species	Loganiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20382	Ramalina paludosa	Species	Ramalinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20897	Suberites domuncula	Species	Suberitidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20091	Iotrochota baculifera	Species	Iotrochotidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27363	Gynochthodes officinalis	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18516	Aplysilla spinifera	Species	Darwinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23186	Verbena bonariensis	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20647	Eugenia myrcianthes	Species	Myrtaceae	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 NPC273548 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	18192
0.1-0.2	30380
0.2-0.3	1141
0.3-0.4	119
0.4-0.5	14
0.5-0.6	11
0.6-0.7	2
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
0.6986	Remote Similarity	NPC201820
0.6053	Remote Similarity	NPC470555
0.5625	Remote Similarity	NPC141822
0.5625	Remote Similarity	NPC1220
0.5625	Remote Similarity	NPC205797
0.5625	Remote Similarity	NPC142563
0.5625	Remote Similarity	NPC241165
0.5556	Remote Similarity	NPC139595
0.5556	Remote Similarity	NPC60704
0.5542	Remote Similarity	NPC293642
0.5443	Remote Similarity	NPC38153
0.5443	Remote Similarity	NPC221173
0.5316	Remote Similarity	NPC291551

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC273548 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2810
0.1-0.2	6298
0.2-0.3	40
0.3-0.4	0
0.4-0.5	0
0.5-0.6	2
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
0.5625	Remote Similarity	NPD5123	Phase 1
0.5625	Remote Similarity	NPD5124	Phase 1

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