NPASS Compound

Natural Product: NPC603245

Natural Product ID	NPC603245
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HBGGXOJOCNVPFY-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1905899
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 72 72 0 0 0 0 0 0 0 0999 V2000 -6.1255 3.1654 -0.5971 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1724 2.0956 -0.7676 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2319 2.1776 0.3209 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6652 0.7207 -0.9717 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8413 0.1000 0.0819 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5659 0.7619 0.4566 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9302 -0.1306 1.5456 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6117 0.4759 1.9856 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9818 -0.3775 3.0470 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7298 -1.6790 2.6116 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8411 -1.9065 1.5550 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3156 -0.9215 1.0594 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6132 -3.2653 1.1348 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3196 -4.2840 1.8155 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1806 -5.6047 1.4937 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3138 -5.8952 0.4681 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3834 -4.9270 -0.2083 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2448 -3.5653 0.1182 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0327 -2.6205 -0.6571 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7887 -3.1096 -1.5861 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1006 -1.2643 -0.5547 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9010 -0.4423 -1.3507 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3670 -0.7952 -1.1172 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1528 0.1640 -2.0286 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6338 -0.0580 -1.9386 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1133 0.1891 -0.5484 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9532 1.5546 -0.0130 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7075 2.6631 -0.6352 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2154 2.4464 -0.5744 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3629 3.0741 -2.0167 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4214 4.0847 -1.2032 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0903 3.5800 0.4473 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1555 2.8814 -1.0076 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7399 2.3614 -1.7140 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3663 3.2182 0.6776 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0017 1.4613 1.1314 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2380 1.8647 -0.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5575 0.0515 -1.1257 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1120 0.6863 -1.9411 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4032 -0.1087 1.0234 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5612 -0.9320 -0.2998 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7493 1.7339 1.0065 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8173 0.8552 -0.3323 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7784 -1.1156 1.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6136 -0.2712 2.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8209 1.4841 2.4231 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9894 0.6130 1.1020 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9849 0.0673 3.3078 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6143 -0.3463 3.9391 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9982 -4.0380 2.6208 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7221 -6.3843 2.0157 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1943 -6.9482 0.2016 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0616 -5.1881 -1.0150 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6393 -0.5491 -2.4276 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7139 0.6271 -1.1088 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6435 -0.5975 -0.0583 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6341 -1.8115 -1.3760 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8086 -0.0476 -3.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8961 1.1825 -1.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1371 0.6080 -2.6385 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8406 -1.1289 -2.2274 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6081 -0.5095 0.1847 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1853 -0.1642 -0.5097 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1902 1.5757 1.0985 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8523 1.8404 -0.0398 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5636 3.6032 0.0085 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4586 2.0599 0.4231 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5474 1.7644 -1.4072 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6843 3.4435 -0.6865 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3437 2.8350 -2.3384 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1579 2.6986 -2.7165 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4461 4.2173 -2.0841 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 1 0 5 6 1 0 6 7 1 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 19 20 2 0 19 21 1 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 28 29 1 0 28 30 1 0 18 13 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 0 3 35 1 0 3 36 1 0 3 37 1 0 4 38 1 0 4 39 1 0 5 40 1 0 5 41 1 0 6 42 1 0 6 43 1 0 7 44 1 0 7 45 1 0 8 46 1 0 8 47 1 0 9 48 1 0 9 49 1 0 14 50 1 0 15 51 1 0 16 52 1 0 17 53 1 0 22 54 1 0 22 55 1 0 23 56 1 0 23 57 1 0 24 58 1 0 24 59 1 0 25 60 1 0 25 61 1 0 26 62 1 0 26 63 1 0 27 64 1 0 27 65 1 0 28 66 1 0 29 67 1 0 29 68 1 0 29 69 1 0 30 70 1 0 30 71 1 0 30 72 1 0 M END

Standard InCHIKey	HBGGXOJOCNVPFY-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C26H42O4/c1-21(2)15-9-5-7-13-19-29-25(27)23-17-11-12-18-24(23)26(28)30-20-14-8-6-10-16-22(3)4/h11-12,17-18,21-22H,5-10,13-16,19-20H2,1-4H3
SMILES	CC(C)CCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCC(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	418.31	Volume:	471.674 ? Van der Waals volume.
Dense:	0.887	LogP:	7.708 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.188 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-7.026 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	8.0
TPSA:	52.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.21	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.143	Fsp³:	0.692
MCE-18:	9.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.714	Fluc inhibitor:	0.585 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.119 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.824	Promiscuous compounds:	0.034

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.149	MDCK Permeability:	-4.708
Pgp-inhibitor:	0.012	Pgp-substrate:	0.0
PAMPA:	0.005 ? 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):	0.0
20% Bioavailability (F20%):	0.008	30% Bioavailability (F30%):	0.283
50% Bioavailability (F50%):	0.255

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.438	MRP1:	0.992
Plasma Protein Binding (PPB):	98.145%	Volume Distribution (VD):	0.887
Fu:	2.67% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.234
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.013
BSEP inhibitor:	0.208

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.748
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.979
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

5.93

Half-life (T1/2):

0.273

ADMET: Toxicity

hERG Blockers:	0.386	hERG Blockers (10um):	0.884
Human Hepatotoxicity (H-HT):	0.04	Drug-induced Liver Injury (DILI):	0.156
AMES Toxicity:	0.024	Rat Oral Acute Toxicity:	0.025
Maximum Recommended Daily Dose:	0.041	Skin Sensitization:	0.726
Carcinogencity:	0.854	Eye Corrosion:	0.436
Eye Irritation:	0.995	Respiratory Toxicity:	0.048
Drug-induced Neurotoxicity:	0.037	Ototoxicity:	0.095
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.021
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.086
A549 Cytotoxicity:	0.034	Hek293 Cytotoxicity:	0.091
BCF:	0.592 ? 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:	3.704 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.63 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.561 ? 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
NPO59199	Haloxylon stocksii	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37175255]
NPO43258	Asystasia gangetica	Species	Acanthaceae	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
NPO59199	Haloxylon stocksii	n.a.	n.a.	0.18	n.a.	n.a.	%	PMID[37175255]

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
Potency	2

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	3063.8	nM	PubChem BioAssay data set
NPT46	Individual protein	Thyroid hormone receptor beta-1	Homo sapiens	Potency	n.a.	398.1	nM	PubChem BioAssay data set

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 NPC603245 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	15916
0.1-0.2	32147
0.2-0.3	1687
0.3-0.4	68
0.4-0.5	17
0.5-0.6	14
0.6-0.7	3
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9697	High Similarity	NPC270699
0.8	Intermediate Similarity	NPC93084
0.8	Intermediate Similarity	NPC251854
0.8	Intermediate Similarity	NPC601045
0.7429	Intermediate Similarity	NPC604461
0.6857	Remote Similarity	NPC10251
0.6279	Remote Similarity	NPC196246
0.6154	Remote Similarity	NPC78701
0.5957	Remote Similarity	NPC254832
0.5957	Remote Similarity	NPC29317
0.5476	Remote Similarity	NPC305912
0.5476	Remote Similarity	NPC1082
0.5429	Remote Similarity	NPC119271
0.5405	Remote Similarity	NPC214067
0.5385	Remote Similarity	NPC146351
0.5385	Remote Similarity	NPC608938
0.5333	Remote Similarity	NPC604244
0.5098	Remote Similarity	NPC71108
0.5098	Remote Similarity	NPC204257
0.5098	Remote Similarity	NPC267539
0.5098	Remote Similarity	NPC229638
0.5098	Remote Similarity	NPC176102

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603245 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2624
0.1-0.2	6028
0.2-0.3	476
0.3-0.4	17
0.4-0.5	3
0.5-0.6	1
0.6-0.7	1
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
0.6857	Remote Similarity	NPD2182	Pre-clinical
0.5098	Remote Similarity	NPD2672	Discontinued

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