NPASS Compound

Natural Product: NPC472583

Natural Product ID	NPC472583
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HRRWPOOLLFZIQU-MOPGFXCFSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3577248
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0003530] Pyranoisoflavonoids

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 44 47 0 0 0 0 0 0 0 0999 V2000 -4.5386 0.5701 -1.4951 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3937 0.3701 -0.0239 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9155 -0.9999 0.3595 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5159 -1.2872 -0.0750 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6163 -0.1344 0.2572 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1634 1.0860 0.5480 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5380 1.3248 0.5532 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3525 2.1633 0.8574 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0116 1.9817 0.8663 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6183 0.7760 0.5818 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2466 -0.2815 0.2752 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0546 0.6010 0.5953 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8579 1.0914 1.5960 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1805 0.9050 1.5659 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7628 0.2542 0.5928 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0436 -0.2758 -0.4563 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6583 -0.0845 -0.4316 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0064 -0.5665 -1.3854 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6779 -0.9535 -1.4637 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0598 -1.1209 -1.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8011 -0.5990 -0.4085 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1405 0.0708 0.5799 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1925 -0.7746 -0.4053 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4215 -1.6653 -1.3956 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7417 -2.0003 -0.1177 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7752 0.5538 0.6002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5093 1.6824 -1.6815 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7712 0.1039 -2.1117 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5589 0.2605 -1.8372 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9340 -1.0477 1.4776 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1569 -2.1603 0.5454 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8047 3.1412 1.0899 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6595 2.8136 1.1061 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1551 -1.2583 0.0410 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3841 1.6329 2.4078 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0847 -1.3642 -2.2845 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5237 -1.6585 -2.2564 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6983 0.4841 1.3975 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7096 -0.1240 0.1836 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3460 -2.6382 -1.5306 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6729 -2.7693 0.5335 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0582 1.6109 0.3992 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7188 0.3669 1.7005 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5308 -0.0809 0.0977 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 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 4 24 1 0 3 25 1 0 2 26 1 0 7 2 1 0 11 5 1 0 17 12 1 0 22 15 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 4 31 1 0 8 32 1 0 9 33 1 0 11 34 1 0 13 35 1 0 19 36 1 0 20 37 1 0 22 38 1 0 23 39 1 0 24 40 1 0 25 41 1 0 26 42 1 0 26 43 1 0 26 44 1 0 M END

Standard InCHIKey	HRRWPOOLLFZIQU-MOPGFXCFSA-N
Standard InCHI	InChI=1S/C20H18O6/c1-20(2)19(24)18(23)13-7-10(3-6-15(13)26-20)14-9-25-16-8-11(21)4-5-12(16)17(14)22/h3-9,18-19,21,23-24H,1-2H3/t18-,19+/m1/s1
SMILES	CC1(C(C(C2=C(O1)C=CC(=C2)C3=COC4=C(C3=O)C=CC(=C4)O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.11	Volume:	351.9 ? Van der Waals volume.
Dense:	1.006	LogP:	1.719 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.809 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.039 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	23.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.621	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.38	Fsp³:	0.25
MCE-18:	81.0 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.311	Fluc inhibitor:	0.678 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.956 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.352 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.28	Promiscuous compounds:	0.139

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.412	MDCK Permeability:	-4.774
Pgp-inhibitor:	0.008	Pgp-substrate:	0.762
PAMPA:	0.685 ? 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):	0.039
20% Bioavailability (F20%):	0.547	30% Bioavailability (F30%):	0.941
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.745
Plasma Protein Binding (PPB):	80.88%	Volume Distribution (VD):	0.211
Fu:	21.247% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.242
OATP1B3 inhibitor:	0.953	BCRP inhibitor:	0.886
BSEP inhibitor:	0.623

ADMET: Metabolism

CYP1A2-inhibitor:	0.022	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.087
CYP2D6-inhibitor:	0.009	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.984
HLM stability:	0.001 ? 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):

7.22

Half-life (T1/2):

1.533

ADMET: Toxicity

hERG Blockers:	0.2	hERG Blockers (10um):	0.581
Human Hepatotoxicity (H-HT):	0.495	Drug-induced Liver Injury (DILI):	0.56
AMES Toxicity:	0.643	Rat Oral Acute Toxicity:	0.593
Maximum Recommended Daily Dose:	0.791	Skin Sensitization:	0.046
Carcinogencity:	0.698	Eye Corrosion:	0.001
Eye Irritation:	0.855	Respiratory Toxicity:	0.673
Drug-induced Neurotoxicity:	0.285	Ototoxicity:	0.595
Hematotoxicity:	0.112	Drug-induced Nephrotoxicity:	0.242
Genotoxicity:	0.811	RPMI-8226 Immunitoxicity:	0.059
A549 Cytotoxicity:	0.186	Hek293 Cytotoxicity:	0.589
BCF:	0.772 ? 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:	3.524 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.205 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.422 ? 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
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	seeds	n.a.	n.a.	PMID[18359631]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[25710081]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3069958]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	seed	n.a.	PMID[8759164]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30150	Psoralea corylifolia	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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	2

Activity Type	# Activity
Cell line	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
NPT81	Cell line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[11720535]
NPT111	Cell line	K562	Homo sapiens	IC50	>	10000.0	nM	PMID[17438054]

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 NPC472583 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	16938
0.1-0.2	29883
0.2-0.3	2677
0.3-0.4	269
0.4-0.5	61
0.5-0.6	21
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC223701
0.7465	Intermediate Similarity	NPC7989
0.7083	Intermediate Similarity	NPC285623
0.6622	Remote Similarity	NPC104406
0.6351	Remote Similarity	NPC149875
0.6029	Remote Similarity	NPC209560
0.6029	Remote Similarity	NPC490700
0.5857	Remote Similarity	NPC12377
0.5775	Remote Similarity	NPC80710
0.5714	Remote Similarity	NPC266572
0.5616	Remote Similarity	NPC35544
0.56	Remote Similarity	NPC215311
0.5455	Remote Similarity	NPC234560
0.5375	Remote Similarity	NPC108859
0.5352	Remote Similarity	NPC203747
0.5352	Remote Similarity	NPC609386
0.5342	Remote Similarity	NPC139364
0.5301	Remote Similarity	NPC258035
0.5294	Remote Similarity	NPC242893
0.527	Remote Similarity	NPC200060
0.5185	Remote Similarity	NPC609101
0.5147	Remote Similarity	NPC212767
0.5135	Remote Similarity	NPC12175
0.5135	Remote Similarity	NPC195763
0.5135	Remote Similarity	NPC191741
0.507	Remote Similarity	NPC487215
0.5067	Remote Similarity	NPC55162
0.5062	Remote Similarity	NPC107838

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472583 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3176
0.1-0.2	5888
0.2-0.3	81
0.3-0.4	3
0.4-0.5	2
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