NPASS Compound

Natural Product: NPC604559

Natural Product ID	NPC604559
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	GJJGHNLSGRQDSD-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2159579
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 73 74 0 0 0 0 0 0 0 0999 V2000 -9.9642 -1.6245 1.7926 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7684 -0.7876 1.3708 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3628 -1.0483 -0.0371 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2027 -0.1862 -0.4244 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0296 -0.4700 0.4637 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8205 0.3898 0.0457 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6980 0.0655 0.9776 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4425 0.8022 0.6976 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4385 0.1408 0.0273 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2240 0.7460 -0.3059 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6985 -0.0285 -0.9776 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9009 -0.4491 -0.3952 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0963 -0.0733 0.7612 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7656 -1.2745 -1.2245 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5945 -2.6445 -1.1362 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6538 -3.1522 -0.2159 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3127 -3.5197 -1.9169 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2216 -3.0167 -2.8055 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9929 -3.8461 -3.6377 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4314 -1.6654 -2.9337 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6832 -0.7902 -2.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9091 0.6499 -2.2097 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9869 1.2885 -1.4532 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1406 1.1947 -0.0035 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4422 -0.1218 0.6085 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7334 -0.7231 0.0526 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9293 0.1615 0.2849 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2019 0.4353 1.7283 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0484 2.0562 0.0627 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0474 2.7171 0.7318 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8609 4.0334 1.0982 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2629 2.1039 1.0627 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2416 2.8963 1.7791 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1047 3.5900 1.2114 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2120 2.8791 3.1836 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.8465 -0.9365 1.8179 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7931 -2.1145 2.7520 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1517 -2.3718 1.0010 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9953 0.2768 1.4925 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9537 -1.0371 2.0849 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0284 -2.1055 -0.2041 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2155 -0.8154 -0.7164 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9826 -0.4072 -1.4938 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4929 0.8900 -0.4177 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2124 -0.2897 1.5208 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7746 -1.5447 0.3451 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6028 0.0384 -1.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0914 1.4344 -0.0446 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5164 -1.0337 0.8772 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9607 0.3184 2.0447 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5971 -0.9115 -0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9226 -2.5167 0.1393 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1717 -4.5788 -1.8416 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8056 -3.9166 -4.6299 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1458 -1.2572 -3.6283 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9344 1.2123 -2.0310 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1099 0.8521 -3.3229 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9244 2.4167 -1.7123 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9635 0.9751 -1.9895 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9751 1.8929 0.3305 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2461 1.6042 0.5558 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6585 -0.8443 0.7027 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7308 0.1194 1.6978 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8993 -1.6545 0.6523 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6673 -0.9712 -1.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8167 1.1500 -0.2393 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8305 -0.2999 -0.1841 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2952 0.3065 1.9448 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6280 -0.2548 2.3639 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9559 1.4744 1.9712 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8608 2.5826 -0.1631 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3357 4.8157 0.7157 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9574 3.2093 3.7480 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 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 10 29 2 0 29 30 1 0 30 31 1 0 30 32 2 0 32 33 1 0 33 34 2 0 33 35 1 0 32 8 1 0 21 14 1 0 1 36 1 0 1 37 1 0 1 38 1 0 2 39 1 0 2 40 1 0 3 41 1 0 3 42 1 0 4 43 1 0 4 44 1 0 5 45 1 0 5 46 1 0 6 47 1 0 6 48 1 0 7 49 1 0 7 50 1 0 9 51 1 0 16 52 1 0 17 53 1 0 19 54 1 0 20 55 1 0 22 56 1 0 22 57 1 0 23 58 1 0 23 59 1 0 24 60 1 0 24 61 1 0 25 62 1 0 25 63 1 0 26 64 1 0 26 65 1 0 27 66 1 0 27 67 1 0 28 68 1 0 28 69 1 0 28 70 1 0 29 71 1 0 31 72 1 0 35 73 1 0 M END

Standard InCHIKey	GJJGHNLSGRQDSD-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H38O7/c1-3-5-7-9-11-13-19-15-21(29)17-23(30)26(19)28(34)35-22-16-20(14-12-10-8-6-4-2)25(27(32)33)24(31)18-22/h15-18,29-31H,3-14H2,1-2H3,(H,32,33)
SMILES	CCCCCCCc1cc(OC(=O)c2c(O)cc(O)cc2CCCCCCC)cc(O)c1C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	486.26	Volume:	516.171 ? Van der Waals volume.
Dense:	0.942	LogP:	8.02 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.601 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.552 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	14.0
TPSA:	124.29 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.125	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.697	Fsp³:	0.5
MCE-18:	16.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.832	Fluc inhibitor:	0.687 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.241 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.524 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.377	Promiscuous compounds:	0.316

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.125	MDCK Permeability:	-4.743
Pgp-inhibitor:	0.308	Pgp-substrate:	0.04
PAMPA:	0.308 ? 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):	0.6
20% Bioavailability (F20%):	0.915	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	0.921

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.96
Plasma Protein Binding (PPB):	99.256%	Volume Distribution (VD):	0.64
Fu:	0.541% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.721
OATP1B3 inhibitor:	0.981	BCRP inhibitor:	0.758
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.474
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.233
CYP2D6-inhibitor:	0.46	CYP2D6-substrate:	0.999
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.187
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.868 ? 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):

1.105

Half-life (T1/2):

1.587

ADMET: Toxicity

hERG Blockers:	0.511	hERG Blockers (10um):	0.629
Human Hepatotoxicity (H-HT):	0.354	Drug-induced Liver Injury (DILI):	0.528
AMES Toxicity:	0.022	Rat Oral Acute Toxicity:	0.127
Maximum Recommended Daily Dose:	0.126	Skin Sensitization:	0.962
Carcinogencity:	0.011	Eye Corrosion:	0.697
Eye Irritation:	0.998	Respiratory Toxicity:	0.987
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.461
Hematotoxicity:	0.074	Drug-induced Nephrotoxicity:	0.563
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.95	Hek293 Cytotoxicity:	0.422
BCF:	0.861 ? 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:	4.671 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.117 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.772 ? 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
NPO42861	Exophiala sp.	Species	Herpotrichiellaceae	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
IC50	6

Activity Type	# Activity
Cell line	6

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
NPT397	Cell line	NCI-H460	Homo sapiens	IC50	=	9100.0	nM	PMID[23031589]
NPT1307	Cell line	Calu-1	Homo sapiens	IC50	=	4300.0	nM	PMID[23031589]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	7800.0	nM	PMID[23031589]
NPT461	Cell line	PANC-1	Homo sapiens	IC50	=	8500.0	nM	PMID[23031589]
NPT2257	Cell line	MCF-10A	Homo sapiens	IC50	>	30000.0	nM	PMID[23031589]
NPT369	Cell line	ACHN	Homo sapiens	IC50	=	8200.0	nM	PMID[23031589]

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 NPC604559 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	21036
0.1-0.2	26416
0.2-0.3	2224
0.3-0.4	131
0.4-0.5	31
0.5-0.6	7
0.6-0.7	3
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9333	High Similarity	NPC606753
0.8333	Intermediate Similarity	NPC309979
0.8209	Intermediate Similarity	NPC307780
0.8065	Intermediate Similarity	NPC602325
0.7971	Intermediate Similarity	NPC6923
0.7164	Intermediate Similarity	NPC237208
0.7059	Intermediate Similarity	NPC134621
0.6667	Remote Similarity	NPC29577
0.6212	Remote Similarity	NPC603370
0.6087	Remote Similarity	NPC66404
0.5758	Remote Similarity	NPC105648
0.5507	Remote Similarity	NPC12305
0.5227	Remote Similarity	NPC600747
0.5195	Remote Similarity	NPC606614
0.5111	Remote Similarity	NPC611202
0.5072	Remote Similarity	NPC17840
0.5072	Remote Similarity	NPC247477

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC604559 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3544
0.1-0.2	5384
0.2-0.3	220
0.3-0.4	2
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