NPASS Compound

Natural Product: NPC220078

Natural Product ID	NPC220078
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NJVSYIMNJLJFLD-IBGZPJMESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	42608050
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0003520] Pyranoflavonoids

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 55 59 0 0 0 0 0 0 0 0999 V2000 -5.1594 -1.3840 2.4428 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3254 -1.7177 1.1983 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3092 -2.4023 0.2402 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3404 -2.7278 1.6146 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0590 -2.4892 1.4046 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5549 -1.2744 0.7793 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2034 -1.0428 0.5674 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2631 0.1116 -0.0260 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7347 0.3499 -0.2500 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1300 -0.1866 -1.5964 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2922 -1.1211 -1.5266 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4962 -1.9898 -2.4189 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2455 -1.0750 -0.4265 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5444 -1.5195 -0.5050 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4160 -1.4553 0.5696 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9853 -0.9303 1.7695 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6807 -0.4861 1.8413 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7975 -0.5436 0.7760 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4998 -0.1113 0.8178 O 0 0 0 0 0 0 0 0 0 0 0 0 6.8442 -0.8495 2.8826 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9449 -2.0480 -1.7460 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6802 1.0450 -0.4083 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0384 0.8467 -0.2120 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9805 1.8606 -0.6334 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5479 2.9617 -1.1984 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1021 3.2494 -1.4444 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8651 3.3967 -2.9524 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7847 4.5506 -0.7215 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2677 2.2043 -1.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4642 -0.3274 0.3879 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8001 -0.5759 0.6068 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8097 -2.2682 2.6047 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4600 -1.3030 3.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7676 -0.4759 2.2907 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5992 -3.3549 0.7302 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8675 -2.5490 -0.7529 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2293 -1.7528 0.1852 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7104 -3.6268 2.0772 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3361 -3.2286 1.7093 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5015 -1.7936 0.8789 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8837 1.4694 -0.2916 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4400 0.6222 -2.3025 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2769 -0.7458 -2.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4289 -1.8146 0.4691 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3389 -0.0763 2.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8299 -0.6372 2.6924 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3388 -2.9811 -1.7046 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0284 1.7103 -0.4833 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2280 3.7543 -1.5320 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2166 3.6116 -3.0785 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0259 2.3731 -3.3699 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5143 4.1567 -3.3995 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2531 4.5199 0.2740 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1252 5.4245 -1.2907 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3081 4.6471 -0.5669 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 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 16 20 1 0 14 21 1 0 8 22 2 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 26 28 1 0 26 29 1 0 23 30 2 0 30 31 1 0 31 2 1 0 30 6 1 0 19 9 1 0 29 22 1 0 18 13 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 5 39 1 0 7 40 1 0 9 41 1 6 10 42 1 0 10 43 1 0 15 44 1 0 17 45 1 0 20 46 1 0 21 47 1 0 24 48 1 0 25 49 1 0 27 50 1 0 27 51 1 0 27 52 1 0 28 53 1 0 28 54 1 0 28 55 1 0 M END

Standard InCHIKey	NJVSYIMNJLJFLD-IBGZPJMESA-N
Standard InCHI	InChI=1S/C25H24O6/c1-24(2)7-5-13-9-16(23-15(22(13)30-24)6-8-25(3,4)31-23)19-12-18(28)21-17(27)10-14(26)11-20(21)29-19/h5-11,19,26-27H,12H2,1-4H3/t19-/m0/s1
SMILES	CC1(C)C=Cc2cc([C@@H]3CC(=O)c4c(cc(cc4O3)O)O)c3c(C=CC(C)(C)O3)c2O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.16	Volume:	427.187 ? Van der Waals volume.
Dense:	0.984	LogP:	4.711 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.708 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.303 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	28.0
TPSA:	85.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.662	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.951	Fsp³:	0.32
MCE-18:	103.758 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.954	Fluc inhibitor:	0.651 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.709 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.892 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.353	Promiscuous compounds:	0.41

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.94	MDCK Permeability:	-4.741
Pgp-inhibitor:	0.904	Pgp-substrate:	0.036
PAMPA:	0.124 ? 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%):	0.627	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.348	MRP1:	0.921
Plasma Protein Binding (PPB):	97.646%	Volume Distribution (VD):	0.369
Fu:	2.327% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.987
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.211	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.02	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.897 ? 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):

5.554

Half-life (T1/2):

1.064

ADMET: Toxicity

hERG Blockers:	0.188	hERG Blockers (10um):	0.56
Human Hepatotoxicity (H-HT):	0.754	Drug-induced Liver Injury (DILI):	0.838
AMES Toxicity:	0.894	Rat Oral Acute Toxicity:	0.85
Maximum Recommended Daily Dose:	0.884	Skin Sensitization:	0.882
Carcinogencity:	0.882	Eye Corrosion:	0.001
Eye Irritation:	0.769	Respiratory Toxicity:	0.967
Drug-induced Neurotoxicity:	0.75	Ototoxicity:	0.485
Hematotoxicity:	0.21	Drug-induced Nephrotoxicity:	0.727
Genotoxicity:	0.943	RPMI-8226 Immunitoxicity:	0.232
A549 Cytotoxicity:	0.712	Hek293 Cytotoxicity:	0.782
BCF:	2.12 ? 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:	4.873 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.135 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.401 ? 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
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20815207]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	bark	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	leaf	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	leaf	n.a.	PMID[22207282]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[23806866]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	root bark	University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic	2011-APR	PMID[24901948]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	Konya, Turkey	2007-APR	PMID[24901948]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	leaves	Chungbuk, Korea	n.a.	PMID[25935644]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[25981820]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	latex	n.a.	PMID[27294120]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	Root barks	n.a.	n.a.	PMID[3097265]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28265	Morus alba	Species	Moraceae	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 NPC220078 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	24560
0.1-0.2	22346
0.2-0.3	2371
0.3-0.4	473
0.4-0.5	70
0.5-0.6	26
0.6-0.7	6
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
0.7015	Intermediate Similarity	NPC88964
0.6901	Remote Similarity	NPC111786
0.6866	Remote Similarity	NPC312973
0.6667	Remote Similarity	NPC272502
0.6667	Remote Similarity	NPC118256
0.6571	Remote Similarity	NPC473272
0.6053	Remote Similarity	NPC43319
0.5811	Remote Similarity	NPC161191
0.5733	Remote Similarity	NPC474038
0.5658	Remote Similarity	NPC475784
0.5616	Remote Similarity	NPC301276
0.5513	Remote Similarity	NPC186686
0.5397	Remote Similarity	NPC182421
0.5312	Remote Similarity	NPC32441
0.5312	Remote Similarity	NPC79943
0.5303	Remote Similarity	NPC321011
0.5303	Remote Similarity	NPC294852
0.5303	Remote Similarity	NPC188679
0.5256	Remote Similarity	NPC227579
0.5256	Remote Similarity	NPC214166
0.5143	Remote Similarity	NPC258630
0.5139	Remote Similarity	NPC17170
0.5139	Remote Similarity	NPC109223
0.5139	Remote Similarity	NPC176229
0.5139	Remote Similarity	NPC10937
0.5128	Remote Similarity	NPC214774
0.5077	Remote Similarity	NPC295261
0.5077	Remote Similarity	NPC243083
0.5077	Remote Similarity	NPC13768
0.5077	Remote Similarity	NPC296490
0.5077	Remote Similarity	NPC287246
0.5077	Remote Similarity	NPC12296
0.5065	Remote Similarity	NPC474021

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC220078 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5064
0.1-0.2	4048
0.2-0.3	29
0.3-0.4	6
0.4-0.5	1
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
0.5312	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5077	Remote Similarity	NPD1550	Phase 2

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