NPASS Compound

Natural Product: NPC605730

Natural Product ID	NPC605730
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MHBLZJBTUXXBHD-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL5278310
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 60 65 0 0 0 0 0 0 0 0999 V2000 9.1664 -0.1556 0.3712 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7765 0.7762 -0.6058 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4507 1.1363 -0.8225 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4082 0.5879 -0.0734 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0988 0.9569 -0.3022 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0178 0.3742 0.4901 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2170 0.2940 1.8655 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2460 -0.2287 2.5720 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1243 -0.6696 2.0653 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1461 -1.2103 2.8917 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0435 -1.6810 2.3801 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0289 -2.2281 3.2317 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2424 -1.6029 1.0223 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4999 -2.1011 0.4874 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5912 -1.2669 0.3611 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8121 -1.6895 -0.1419 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9443 -0.7902 -0.2640 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1909 -1.2005 0.1397 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2456 -0.3921 0.0373 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1934 0.8120 -0.4358 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2715 1.6505 -0.5452 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1733 2.9255 -1.0547 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2760 3.7605 -1.1579 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9466 3.4100 -1.4830 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8721 2.5731 -1.3736 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9534 1.2925 -0.8653 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8368 0.4840 -0.7750 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7465 0.9609 -1.1736 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8899 -3.0257 -0.5232 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7991 -3.8573 -0.3963 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5906 -3.4236 0.1057 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5125 -4.3098 0.2140 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6956 -1.0764 0.1655 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8777 -0.6118 0.6988 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8608 -0.0738 -0.0870 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6806 -0.0014 -1.3301 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8478 1.8836 -1.2926 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8905 2.4349 -2.0449 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1994 2.0634 -1.8133 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2659 2.5965 -2.5486 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8323 0.1917 1.3556 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2758 -0.1847 0.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7588 -1.1489 0.1047 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6301 -0.1358 0.6964 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1489 0.6569 2.3136 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2946 -1.2772 3.9750 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7504 -1.5929 3.5156 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5628 -0.2151 0.6507 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3730 -2.1808 0.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2269 1.2741 -0.2120 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1251 3.4727 -0.6886 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8227 4.4096 -1.8917 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9145 2.9454 -1.7057 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8465 -3.3609 -0.9184 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8865 -4.8945 -0.7009 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1305 -4.4873 -0.5210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5051 -1.0278 -0.9221 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8186 2.1712 -1.4697 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6582 3.1614 -2.8163 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1461 2.8460 -2.1119 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 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 11 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 16 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 13 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 5 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 39 3 1 0 35 6 1 0 34 9 1 0 31 14 1 0 27 17 1 0 26 20 1 0 1 41 1 0 1 42 1 0 1 43 1 0 4 44 1 0 7 45 1 0 10 46 1 0 12 47 1 0 15 48 1 0 18 49 1 0 21 50 1 0 23 51 1 0 24 52 1 0 25 53 1 0 29 54 1 0 30 55 1 0 32 56 1 0 33 57 1 0 37 58 1 0 38 59 1 0 40 60 1 0 M END

Standard InCHIKey	MHBLZJBTUXXBHD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C31H20O9/c1-38-29-9-16(3-7-25(29)34)23-14-40-28-12-26(35)20(11-21(28)31(23)37)19-8-15(2-6-24(19)33)22-13-39-27-10-17(32)4-5-18(27)30(22)36/h2-14,32-35H,1H3
SMILES	COc1cc(-c2coc3cc(O)c(-c4cc(-c5coc6cc(O)ccc6c5=O)ccc4O)cc3c2=O)ccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	536.11	Volume:	530.322 ? Van der Waals volume.
Dense:	1.011	LogP:	3.39 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.515 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.036 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	36.0
TPSA:	150.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.221	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.909	Fsp³:	0.032
MCE-18:	35.0 ? 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:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.999	Fluc inhibitor:	0.793 ? 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:	0.973 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.584	Promiscuous compounds:	0.635

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.133	MDCK Permeability:	-4.813
Pgp-inhibitor:	0.001	Pgp-substrate:	0.237
PAMPA:	0.901 ? 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):	0.011
20% Bioavailability (F20%):	0.939	30% Bioavailability (F30%):	0.987
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.556
Plasma Protein Binding (PPB):	95.362%	Volume Distribution (VD):	-0.519
Fu:	4.992% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.991
BSEP inhibitor:	0.889

ADMET: Metabolism

CYP1A2-inhibitor:	0.772	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.97
CYP2C9-inhibitor:	0.994	CYP2C9-substrate:	0.889
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.661
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.99
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.017 ? 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):

2.716

Half-life (T1/2):

1.904

ADMET: Toxicity

hERG Blockers:	0.318	hERG Blockers (10um):	0.657
Human Hepatotoxicity (H-HT):	0.626	Drug-induced Liver Injury (DILI):	0.936
AMES Toxicity:	0.739	Rat Oral Acute Toxicity:	0.82
Maximum Recommended Daily Dose:	0.991	Skin Sensitization:	0.113
Carcinogencity:	0.838	Eye Corrosion:	0.0
Eye Irritation:	0.845	Respiratory Toxicity:	0.874
Drug-induced Neurotoxicity:	0.172	Ototoxicity:	0.396
Hematotoxicity:	0.088	Drug-induced Nephrotoxicity:	0.296
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.276
A549 Cytotoxicity:	0.828	Hek293 Cytotoxicity:	0.943
BCF:	1.244 ? 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:	4.213 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.686 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.329 ? 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
NPO43802	Streptomyces sp. HDN154127	Genus	Streptomycetaceae	Bacteria	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
MIC	14

Activity Type	# Activity
Organism	14

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
NPT5492	Organism	Proteus sp.	Proteus sp.	MIC	=	12000.0	nM	PMID[36535025]
NPT29703	Organism	Mycolicibacterium phlei	Mycolicibacterium phlei	MIC	=	12000.0	nM	PMID[36535025]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	12000.0	nM	PMID[36535025]
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	50000.0	nM	PMID[36535025]
NPT565	Organism	Vibrio parahaemolyticus	Vibrio parahaemolyticus	MIC	=	50000.0	nM	PMID[36535025]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	50000.0	nM	PMID[36535025]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	12000.0	nM	PMID[36535025]

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 NPC605730 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	28506
0.1-0.2	18859
0.2-0.3	2123
0.3-0.4	267
0.4-0.5	72
0.5-0.6	23
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
0.7937	Intermediate Similarity	NPC139364
0.7143	Intermediate Similarity	NPC611071
0.6418	Remote Similarity	NPC203747
0.6232	Remote Similarity	NPC12377
0.6143	Remote Similarity	NPC80710
0.6056	Remote Similarity	NPC109187
0.5942	Remote Similarity	NPC209560
0.5942	Remote Similarity	NPC490700
0.5942	Remote Similarity	NPC609386
0.5915	Remote Similarity	NPC12175
0.5915	Remote Similarity	NPC40290
0.5833	Remote Similarity	NPC254702
0.5833	Remote Similarity	NPC291802
0.5733	Remote Similarity	NPC607759
0.5694	Remote Similarity	NPC156953
0.5694	Remote Similarity	NPC195763
0.5694	Remote Similarity	NPC191741
0.5672	Remote Similarity	NPC242893
0.5606	Remote Similarity	NPC234560
0.5556	Remote Similarity	NPC262623
0.5541	Remote Similarity	NPC35544
0.5513	Remote Similarity	NPC610903
0.5405	Remote Similarity	NPC200060
0.5362	Remote Similarity	NPC235428
0.5278	Remote Similarity	NPC100971
0.52	Remote Similarity	NPC55162
0.52	Remote Similarity	NPC114192
0.5072	Remote Similarity	NPC212767
0.5062	Remote Similarity	NPC149875

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605730 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5342
0.1-0.2	3766
0.2-0.3	36
0.3-0.4	6
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