NPASS Compound

Natural Product: NPC600365

Natural Product ID	NPC600365
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GXCGYHWSYNQVHU-BQVYPXEESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL576350
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 67 71 0 0 0 0 0 0 0 0999 V2000 -5.1311 3.4631 1.0397 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1932 2.3550 0.6187 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7840 1.4932 1.5181 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8430 0.3408 1.2151 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.6437 -0.7429 0.9554 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2106 -1.7698 0.2225 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9739 -2.5225 0.8269 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9214 -1.4562 0.6958 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3512 -1.9547 0.5328 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7320 -3.2534 0.4958 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1055 -4.2246 0.6240 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0956 -3.7028 0.3011 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1160 -2.8931 0.2164 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4483 -3.4379 0.0049 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5702 -2.8169 -0.0900 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8606 -1.4331 -0.0043 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0553 -1.0409 -0.2475 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9514 -0.4515 0.3379 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4160 0.8887 0.3592 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5095 1.8088 1.0319 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0953 1.8580 0.6689 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6462 2.1437 -0.6617 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1894 1.6392 1.5756 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7401 1.6450 1.4112 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0243 1.4178 2.4583 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1157 1.8731 0.2330 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2166 1.8848 -0.0279 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0513 0.6820 0.0215 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1390 0.9403 -1.0841 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7724 2.2755 -0.7923 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3627 -0.5760 -0.4779 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2750 -0.3218 -1.4612 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4761 -1.4023 -1.0831 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9675 -1.5462 -2.3182 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1149 -2.5448 -1.8019 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9359 3.7795 2.0734 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1658 3.0210 1.0236 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1093 4.2828 0.3012 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1557 1.6277 2.5449 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3020 0.2058 2.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0085 -2.4858 0.0363 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8747 -3.3537 0.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1733 -2.8921 1.8164 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8787 -0.8589 1.6490 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3072 -4.7375 0.2196 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9942 -1.8900 0.2955 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5030 -4.5384 -0.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4622 -3.4734 -0.2686 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4160 0.9484 0.8584 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6099 1.2464 -0.6781 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6345 1.8061 2.1638 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8994 2.8685 0.7957 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1351 1.2299 -1.0743 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4714 2.3421 -1.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9129 2.9651 -0.7721 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5899 1.4414 2.5133 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6892 2.6302 0.7003 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4018 2.4463 -1.0222 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9089 0.1895 -0.9281 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6441 0.9522 -2.0627 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2108 3.1493 -1.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7329 2.3008 -1.4072 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1979 0.7362 -1.7856 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6873 -0.6887 -1.0046 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3911 -0.9204 -2.3977 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5348 -1.1109 -3.2493 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0428 -1.8366 -2.5104 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 3 13 14 1 0 14 15 2 3 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 2 3 23 24 1 0 24 25 2 0 24 26 1 0 26 27 1 0 28 27 1 1 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 6 31 33 1 0 33 34 1 0 34 35 1 0 30 2 1 0 33 35 1 6 28 4 1 0 33 6 1 0 31 8 1 0 1 36 1 0 1 37 1 0 1 38 1 0 3 39 1 0 4 40 1 1 6 41 1 6 7 42 1 0 7 43 1 0 8 44 1 1 12 45 1 0 13 46 1 0 14 47 1 0 15 48 1 0 19 49 1 0 19 50 1 0 20 51 1 0 20 52 1 0 22 53 1 0 22 54 1 0 22 55 1 0 23 56 1 0 27 57 1 0 27 58 1 0 29 59 1 0 29 60 1 0 30 61 1 0 30 62 1 0 32 63 1 0 32 64 1 0 32 65 1 0 34 66 1 0 34 67 1 0 M END

Standard InCHIKey	GXCGYHWSYNQVHU-BQVYPXEESA-N
Standard InCHI	InChI=1S/C27H32O8/c1-17-8-10-26-15-32-24(30)13-18(2)9-11-31-22(28)6-4-5-7-23(29)35-19-14-21(34-20(26)12-17)27(16-33-27)25(19,26)3/h4-7,12-13,19-21H,8-11,14-16H2,1-3H3/t19-,20-,21-,25-,26-,27+/m1/s1
SMILES	CC1=C[C@H]2O[C@@H]3C[C@H]4OC(=O)C=CC=CC(=O)OCCC(C)=CC(=O)OC[C@@]2(CC1)[C@]4(C)[C@]31CO1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	484.21	Volume:	484.632 ? Van der Waals volume.
Dense:	0.999	LogP:	1.109 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.432 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.229 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	36.0
TPSA:	100.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.224	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.858	Fsp³:	0.593
MCE-18:	115.349 ? 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:	0.92	Fluc inhibitor:	0.051 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.037 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.167 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.341	Promiscuous compounds:	0.349

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.944	MDCK Permeability:	-4.652
Pgp-inhibitor:	0.003	Pgp-substrate:	0.303
PAMPA:	0.994 ? 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):	0.002
20% Bioavailability (F20%):	0.018	30% Bioavailability (F30%):	0.045
50% Bioavailability (F50%):	0.325

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.619	MRP1:	0.923
Plasma Protein Binding (PPB):	95.815%	Volume Distribution (VD):	-0.011
Fu:	4.613% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.979	BCRP inhibitor:	0.0
BSEP inhibitor:	0.587

ADMET: Metabolism

CYP1A2-inhibitor:	0.116	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.07	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.175	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.003
HLM stability:	0.548 ? 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):

3.604

Half-life (T1/2):

2.417

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.471
Human Hepatotoxicity (H-HT):	0.225	Drug-induced Liver Injury (DILI):	0.965
AMES Toxicity:	0.804	Rat Oral Acute Toxicity:	0.967
Maximum Recommended Daily Dose:	0.926	Skin Sensitization:	1.0
Carcinogencity:	0.642	Eye Corrosion:	0.879
Eye Irritation:	0.993	Respiratory Toxicity:	0.804
Drug-induced Neurotoxicity:	0.693	Ototoxicity:	0.543
Hematotoxicity:	0.753	Drug-induced Nephrotoxicity:	0.965
Genotoxicity:	0.982	RPMI-8226 Immunitoxicity:	0.433
A549 Cytotoxicity:	0.037	Hek293 Cytotoxicity:	0.076
BCF:	0.669 ? 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:	3.466 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.463 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.729 ? 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
NPO52111	Stachybotrys atra	Genus	Stachybotryaceae	Eukaryota	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
EC50	2
IFI	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	2
Unchecked	1

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
NPT1229	Cell line	Huh-7	Homo sapiens	CC50	=	206.4	nM	PMID[18579783]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	EC50	=	3.91	nM	PMID[18579783]
NPT28438	Unchecked	Unchecked	n.a.	IFI	=	22.64	%	PMID[18579783]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	EC50	=	9.18	nM	PMID[18579783]

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 NPC600365 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	23843
0.1-0.2	25098
0.2-0.3	848
0.3-0.4	23
0.4-0.5	11
0.5-0.6	8
0.6-0.7	14
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC98813
0.8594	High Similarity	NPC484152
0.8235	Intermediate Similarity	NPC13743
0.8116	Intermediate Similarity	NPC29389
0.8116	Intermediate Similarity	NPC112316
0.726	Intermediate Similarity	NPC108682
0.72	Intermediate Similarity	NPC484149
0.7083	Intermediate Similarity	NPC469959
0.7083	Intermediate Similarity	NPC469957
0.7083	Intermediate Similarity	NPC98038
0.7083	Intermediate Similarity	NPC313921
0.7067	Intermediate Similarity	NPC484923
0.7067	Intermediate Similarity	NPC484922
0.6857	Remote Similarity	NPC265502
0.68	Remote Similarity	NPC472263
0.675	Remote Similarity	NPC484153
0.675	Remote Similarity	NPC484925
0.6456	Remote Similarity	NPC474286
0.6456	Remote Similarity	NPC484150
0.6456	Remote Similarity	NPC484155
0.6316	Remote Similarity	NPC9579
0.622	Remote Similarity	NPC475130
0.622	Remote Similarity	NPC484145
0.622	Remote Similarity	NPC484151
0.619	Remote Similarity	NPC484154
0.6125	Remote Similarity	NPC101965
0.6125	Remote Similarity	NPC101400
0.5897	Remote Similarity	NPC469960
0.5897	Remote Similarity	NPC93026
0.5846	Remote Similarity	NPC234293
0.5783	Remote Similarity	NPC484144
0.5625	Remote Similarity	NPC484920
0.557	Remote Similarity	NPC65700
0.5488	Remote Similarity	NPC484924
0.5231	Remote Similarity	NPC94915

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC600365 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7510
0.1-0.2	1630
0.2-0.3	10
0.3-0.4	0
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