NPASS Compound

Natural Product: NPC471398

Natural Product ID	NPC471398
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JJXDFSOHRJHKGE-SEXHSVSSSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2431873
PubChem CID	73356967
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001560] Withanolides and derivatives

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 71 76 0 0 0 0 0 0 0 0999 V2000 -8.2227 -0.6291 -0.7761 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0211 -0.3072 -0.7159 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2747 -0.1745 -1.9610 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0108 0.1662 -1.8655 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2605 0.4300 -0.6467 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0393 0.2882 0.6052 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3082 -0.0525 0.5313 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3616 0.5287 1.8771 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9347 0.0660 1.9190 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2130 0.1909 0.5972 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0492 -0.4584 -0.4498 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3650 -0.7270 -1.7446 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0997 -1.5393 -1.4869 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2114 -0.6938 -0.6428 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9243 -0.5289 0.7074 C 0 0 1 0 0 0 0 0 0 0 0 0 0.1445 0.0992 1.5224 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4323 -0.5760 1.0188 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0457 -1.3748 -0.1718 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0777 -1.5724 -1.2022 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5928 -3.0187 -1.1974 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2201 -0.6180 -1.1852 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4824 0.0315 0.1298 C 0 0 1 0 0 0 0 0 0 0 0 0 2.3494 0.4076 0.8127 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4085 -0.6833 0.9260 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2096 0.1963 1.6391 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0652 -0.0899 2.5093 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8907 1.5728 1.2022 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2613 1.3162 -0.1602 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3853 1.0402 -1.1389 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0894 2.4413 1.0175 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3806 -1.3321 -1.5653 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0385 0.6104 -1.3209 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8391 1.9038 -0.7010 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7364 -0.3479 -2.9237 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4638 0.2616 -2.8092 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9283 -0.1696 1.4370 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8956 0.0273 2.7193 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4216 1.6243 2.1105 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8730 -0.9668 2.3154 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3934 0.7151 2.6447 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0411 1.2801 0.4371 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4099 -1.4322 -0.0419 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1650 0.1745 -2.3491 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0249 -1.3831 -2.3511 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5910 -1.7906 -2.4404 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4301 -2.4813 -0.9838 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1102 -1.5605 1.0639 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1677 1.1892 1.2847 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0181 -0.0676 2.5865 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7689 -1.2335 1.8581 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7223 -2.3910 0.2012 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5810 -1.4667 -2.2131 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5606 -3.0828 -0.6588 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7852 -3.3789 -2.2292 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8530 -3.7082 -0.7476 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1143 0.1688 -1.9861 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1621 2.0270 1.9093 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6119 2.1370 -0.4686 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0544 1.9118 -1.1596 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0229 0.8770 -2.1615 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9642 0.1847 -0.7279 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7856 3.2826 0.3269 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9700 1.8983 0.6632 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3230 2.9718 1.9867 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1755 -1.8833 -2.3816 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0453 1.0301 -1.1302 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6863 1.3918 -1.0807 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0164 0.4099 -2.4325 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6916 2.4545 -1.1982 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9707 2.0676 -1.3415 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7721 2.3457 0.3079 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 22 23 1 1 22 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 1 0 28 29 1 0 27 30 1 0 21 31 1 0 14 32 1 6 5 33 1 6 7 2 1 0 15 10 1 0 23 17 1 0 11 5 1 0 18 14 1 0 28 22 1 0 3 34 1 0 4 35 1 0 7 36 1 0 8 37 1 0 8 38 1 0 9 39 1 0 9 40 1 0 10 41 1 6 11 42 1 1 12 43 1 0 12 44 1 0 13 45 1 0 13 46 1 0 15 47 1 1 16 48 1 0 16 49 1 0 17 50 1 1 18 51 1 1 19 52 1 6 20 53 1 0 20 54 1 0 20 55 1 0 21 56 1 6 27 57 1 1 28 58 1 6 29 59 1 0 29 60 1 0 29 61 1 0 30 62 1 0 30 63 1 0 30 64 1 0 31 65 1 0 32 66 1 0 32 67 1 0 32 68 1 0 33 69 1 0 33 70 1 0 33 71 1 0 M END

Standard InCHIKey	JJXDFSOHRJHKGE-SEXHSVSSSA-N
Standard InCHI	InChI=1S/C28H38O5/c1-14-16(3)28(33-25(14)31)24(30)15(2)23-22(32-28)13-21-19-7-6-17-12-18(29)8-10-26(17,4)20(19)9-11-27(21,23)5/h8,10,12,14-16,19-24,30H,6-7,9,11,13H2,1-5H3/t14-,15-,16+,19+,20-,21-,22-,23-,24-,26-,27-,28-/m0/s1
SMILES	O=C1C=C[C@]2(C(=C1)CC[C@@H]1[C@@H]2CC[C@]2([C@H]1C[C@H]1[C@@H]2[C@H](C)[C@@H]([C@@]2(O1)OC(=O)[C@H]([C@H]2C)C)O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	454.27	Volume:	474.911 ? Van der Waals volume.
Dense:	0.957	LogP:	2.807 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.008 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.746 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	32.0
TPSA:	72.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	6.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.548	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.676	Fsp³:	0.786
MCE-18:	143.52 ? 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:	0.73	Fluc inhibitor:	0.046 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.142 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.144	Promiscuous compounds:	0.723

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.273	MDCK Permeability:	-4.852
Pgp-inhibitor:	0.709	Pgp-substrate:	0.04
PAMPA:	0.662 ? 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%):	0.12	30% Bioavailability (F30%):	0.241
50% Bioavailability (F50%):	0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.022	MRP1:	0.895
Plasma Protein Binding (PPB):	91.612%	Volume Distribution (VD):	0.309
Fu:	9.646% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.046
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.013	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.307	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.01
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.275
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.715 ? 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):

12.382

Half-life (T1/2):

1.851

ADMET: Toxicity

hERG Blockers:	0.08	hERG Blockers (10um):	0.515
Human Hepatotoxicity (H-HT):	0.732	Drug-induced Liver Injury (DILI):	0.25
AMES Toxicity:	0.247	Rat Oral Acute Toxicity:	0.736
Maximum Recommended Daily Dose:	0.935	Skin Sensitization:	0.981
Carcinogencity:	0.775	Eye Corrosion:	0.005
Eye Irritation:	0.587	Respiratory Toxicity:	0.95
Drug-induced Neurotoxicity:	0.134	Ototoxicity:	0.8
Hematotoxicity:	0.229	Drug-induced Nephrotoxicity:	0.355
Genotoxicity:	0.765	RPMI-8226 Immunitoxicity:	0.253
A549 Cytotoxicity:	0.021	Hek293 Cytotoxicity:	0.47
BCF:	1.705 ? 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:	4.159 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.637 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.174 ? 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
NPO25915	Sinularia dura	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18630962]
NPO25915	Sinularia dura	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[24128077]
NPO25915	Sinularia dura	Species	Alcyoniidae	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
ED50	2
IC50	4

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
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	7.5	uM	PMID[11421731]
NPT112	Cell line	MOLT-4	Homo sapiens	ED50	=	9.9	uM	PMID[16562846]
NPT112	Cell line	MOLT-4	Homo sapiens	IC50	=	13700.0	nM	PMID[28648460]
NPT168	Cell line	P388	Mus musculus	IC50	=	18300.0	nM	PMID[28648460]
NPT111	Cell line	K562	Homo sapiens	IC50	=	17400.0	nM	PMID[28648460]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	20500.0	nM	PMID[28648460]

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 NPC471398 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	18007
0.1-0.2	28073
0.2-0.3	3640
0.3-0.4	110
0.4-0.5	13
0.5-0.6	8
0.6-0.7	3
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC604986
0.7042	Intermediate Similarity	NPC600537
0.6164	Remote Similarity	NPC164835
0.6164	Remote Similarity	NPC228669
0.6053	Remote Similarity	NPC601481
0.589	Remote Similarity	NPC255309
0.5541	Remote Similarity	NPC608739
0.5224	Remote Similarity	NPC92327
0.5205	Remote Similarity	NPC474463
0.52	Remote Similarity	NPC218301
0.5143	Remote Similarity	NPC6434
0.5139	Remote Similarity	NPC105197
0.5062	Remote Similarity	NPC96377

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471398 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6804
0.1-0.2	2084
0.2-0.3	221
0.3-0.4	38
0.4-0.5	3
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