NPASS Compound

Natural Product: NPC605736

Natural Product ID	NPC605736
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GHYDRKXFHRBWGZ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL5438675
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 58 0 0 0 0 0 0 0 0999 V2000 -4.0957 -3.1787 0.7877 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8379 -3.1295 0.0066 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6666 -4.0809 -1.1086 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8870 -2.2395 0.3135 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0511 -1.2820 1.4290 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9523 0.1295 1.0608 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7926 0.7378 0.7085 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5290 0.1471 0.6470 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9617 -0.9830 1.2463 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2478 -1.5215 1.0594 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1475 -0.9009 0.2343 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7416 0.2628 -0.3982 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4853 0.7592 -0.1955 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0946 1.9199 -0.8321 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7153 0.8934 -1.2705 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9184 0.4188 -1.4728 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3666 -0.8163 -0.8094 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6299 -0.4919 -0.0152 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6989 -1.8082 -1.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4147 -1.3896 0.0210 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8994 2.0329 0.3720 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9630 2.7449 0.3496 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9412 4.0950 -0.0218 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0888 4.8338 -0.0376 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0748 6.1976 -0.4115 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2733 4.2291 0.3188 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3217 2.9077 0.6867 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4973 2.2668 1.0516 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1553 2.1599 0.7019 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1590 0.8416 1.0617 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2594 0.3420 1.3757 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6523 -2.2521 0.5740 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7250 -4.0365 0.4789 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9022 -3.3264 1.8873 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9054 -3.5566 -2.0415 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3279 -4.9646 -0.9931 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6312 -4.4856 -1.1550 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0045 -2.2530 -0.2954 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1415 -1.4429 1.8329 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4964 -1.5525 2.3115 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3655 -1.5226 1.9212 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5344 -2.4218 1.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4934 1.8150 -1.6479 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4331 1.8033 -1.7808 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6076 0.9529 -2.1517 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4808 0.5116 0.4148 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7920 -1.2005 0.8039 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4683 -0.4271 -0.7184 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7485 -1.7307 -2.2421 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5252 -2.8540 -1.5506 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0193 -1.6902 -2.7911 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0004 4.5430 -0.2963 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4956 6.4700 -1.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1966 4.8034 0.3119 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0240 2.7200 1.8089 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 2 3 4 5 1 0 5 6 1 0 6 7 2 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 13 14 1 0 12 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 7 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 24 26 2 0 26 27 1 0 27 28 1 0 27 29 2 0 29 30 1 0 30 31 2 0 30 6 1 0 13 8 1 0 29 22 1 0 20 11 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 5 40 1 0 9 41 1 0 10 42 1 0 14 43 1 0 15 44 1 0 16 45 1 0 18 46 1 0 18 47 1 0 18 48 1 0 19 49 1 0 19 50 1 0 19 51 1 0 23 52 1 0 25 53 1 0 26 54 1 0 28 55 1 0 M END

Standard InCHIKey	GHYDRKXFHRBWGZ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H24O6/c1-13(2)5-6-17-23(29)21-18(27)11-14(26)12-20(21)30-24(17)16-7-8-19-15(22(16)28)9-10-25(3,4)31-19/h5,7-12,26-28H,6H2,1-4H3
SMILES	CC(C)=CCc1c(-c2ccc3c(c2O)C=CC(C)(C)O3)oc2cc(O)cc(O)c2c1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.16	Volume:	433.107 ? Van der Waals volume.
Dense:	0.97	LogP:	4.794 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.664 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.059 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
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:	0.499	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.262	Fsp³:	0.24
MCE-18:	55.742 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.907	Fluc inhibitor:	0.863 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.919 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.817 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.242	Promiscuous compounds:	0.173

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.145	MDCK Permeability:	-4.783
Pgp-inhibitor:	0.771	Pgp-substrate:	0.278
PAMPA:	0.583 ? 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%):	0.915	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.015	MRP1:	0.939
Plasma Protein Binding (PPB):	96.698%	Volume Distribution (VD):	0.422
Fu:	3.196% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	0.815	BCRP inhibitor:	0.993
BSEP inhibitor:	0.977

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.309	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.632	CYP2C9-substrate:	0.827
CYP2D6-inhibitor:	0.945	CYP2D6-substrate:	0.979
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

2.36

Half-life (T1/2):

1.372

ADMET: Toxicity

hERG Blockers:	0.053	hERG Blockers (10um):	0.523
Human Hepatotoxicity (H-HT):	0.431	Drug-induced Liver Injury (DILI):	0.716
AMES Toxicity:	0.667	Rat Oral Acute Toxicity:	0.834
Maximum Recommended Daily Dose:	0.846	Skin Sensitization:	0.866
Carcinogencity:	0.626	Eye Corrosion:	0.0
Eye Irritation:	0.819	Respiratory Toxicity:	0.97
Drug-induced Neurotoxicity:	0.096	Ototoxicity:	0.224
Hematotoxicity:	0.068	Drug-induced Nephrotoxicity:	0.168
Genotoxicity:	0.979	RPMI-8226 Immunitoxicity:	0.057
A549 Cytotoxicity:	0.396	Hek293 Cytotoxicity:	0.799
BCF:	1.817 ? 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:	4.898 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.53 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.002 ? 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

Activity Type	# Activity
MIC	6
Ratio	4
Activity	11

Activity Type	# Activity
Organism	14
Subcellular	7

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
NPT23195	Subcellular	Cell membrane	Bacteria	Activity	n.a.	n.a.	n.a.	PMID[37499116]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	Ratio	=	8.0	n.a.	PMID[37499116]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	1.0	ug.mL-1	PMID[37499116]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	4.0	ug.mL-1	PMID[37499116]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	Ratio	=	8.0	n.a.	PMID[37499116]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	n.a.	n.a.	n.a.	PMID[37499116]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	1.0	ug.mL-1	PMID[37499116]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Ratio	=	8.0	n.a.	PMID[37499116]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	Ratio	=	8.0	n.a.	PMID[37499116]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	=	1.0	ug.mL-1	PMID[37499116]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	Activity	=	2.0	log10CFU/ml	PMID[37499116]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	1.0	ug.mL-1	PMID[37499116]

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 NPC605736 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	21224
0.1-0.2	24874
0.2-0.3	3013
0.3-0.4	657
0.4-0.5	75
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
0.7051	Intermediate Similarity	NPC603595
0.6301	Remote Similarity	NPC190046
0.6296	Remote Similarity	NPC78803
0.5897	Remote Similarity	NPC482697
0.5833	Remote Similarity	NPC62840
0.5698	Remote Similarity	NPC476637
0.5556	Remote Similarity	NPC231763
0.5488	Remote Similarity	NPC479191
0.5465	Remote Similarity	NPC276444
0.5443	Remote Similarity	NPC37208
0.5422	Remote Similarity	NPC13408
0.5366	Remote Similarity	NPC134796
0.5172	Remote Similarity	NPC218871
0.5057	Remote Similarity	NPC282300

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605736 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3242
0.1-0.2	5834
0.2-0.3	69
0.3-0.4	5
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