NPASS Compound

Natural Product: NPC471281

Natural Product ID	NPC471281
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(4E,20E)-Tetracosa-4,20-Dien-1,23-Diyne-3,22-Diol
IUPAC Name	(4E,20E)-tetracosa-4,20-dien-1,23-diyne-3,22-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2408396
PubChem CID	71745714
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols

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 64 63 0 0 0 0 0 0 0 0999 V2000 9.2344 0.1580 1.7583 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9196 -0.3280 0.4574 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5996 0.2820 0.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5062 1.5533 -0.1977 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2905 2.2784 -0.5822 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0317 1.4084 -0.5081 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7893 0.9684 0.8945 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6083 0.0827 1.0711 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3172 0.8602 0.7197 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1340 -0.0353 1.0489 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1745 0.6530 0.7791 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3711 1.0804 -0.6433 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6320 1.8567 -0.7714 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8631 1.0770 -0.3563 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0141 -0.1522 -1.1756 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2491 -0.9196 -0.8807 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3087 -1.3777 0.5421 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5416 -2.3006 0.6129 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7700 -1.5739 0.3747 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6009 -1.6103 -0.6427 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8096 -0.7275 -0.5292 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4229 -0.6073 -1.8884 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.8951 -0.5130 -2.9841 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7055 -1.3335 0.3446 O 0 0 0 0 0 0 0 0 0 0 0 0 8.7432 -1.8120 0.5611 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6089 -3.0354 0.6621 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1575 -0.6016 2.4016 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7509 -0.1339 -0.1883 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7593 -0.4450 -0.0214 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4207 2.1707 -0.1525 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3631 2.5811 -1.6525 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0848 3.1257 0.0694 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2285 0.5290 -1.2039 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2002 1.9984 -0.9335 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4085 1.9708 1.4192 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6777 0.7589 1.5015 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5334 -0.2274 2.1634 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6583 -0.8593 0.4917 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3257 1.1303 -0.3365 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3754 1.6919 1.4463 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2028 -0.1473 2.1946 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2207 -1.0121 0.6293 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0078 -0.0406 1.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2737 1.5421 1.4792 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5019 1.6271 -1.0782 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4668 0.1839 -1.3184 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8359 2.2316 -1.7736 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6072 2.7400 -0.0728 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7367 1.8011 -0.4417 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8357 0.7941 0.7404 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0275 0.0835 -2.2679 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1274 -0.8422 -0.9786 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4114 -1.7950 -1.5630 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1182 -0.2101 -1.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4514 -1.9753 0.8543 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4360 -0.5628 1.2450 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3202 -3.0962 -0.1072 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4549 -2.7451 1.6487 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0966 -0.9287 1.2458 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4575 -2.1903 -1.5052 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5542 0.2717 -0.1634 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3204 -0.4146 -3.9585 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2591 -0.6275 0.7620 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5044 -4.0710 0.7356 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 1 0 7 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 2 0 20 21 1 0 21 22 1 0 22 23 3 0 21 24 1 0 2 25 1 0 25 26 3 0 1 27 1 0 2 28 1 0 3 29 1 0 4 30 1 0 5 31 1 0 5 32 1 0 6 33 1 0 6 34 1 0 7 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 0 10 42 1 0 11 43 1 0 11 44 1 0 12 45 1 0 12 46 1 0 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 17 56 1 0 18 57 1 0 18 58 1 0 19 59 1 0 20 60 1 0 21 61 1 0 23 62 1 0 24 63 1 0 26 64 1 0 M END

Standard InCHIKey	KJWNXSBXDZJMLB-FLFKKZLDSA-N
Standard InCHI	InChI=1S/C24H38O2/c1-3-23(25)21-19-17-15-13-11-9-7-5-6-8-10-12-14-16-18-20-22-24(26)4-2/h1-2,19-26H,5-18H2/b21-19+,22-20+
SMILES	OC(/C=C/CCCCCCCCCCCCCC/C=C/C(C#C)O)C#C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.29	Volume:	425.422 ? Van der Waals volume.
Dense:	0.842	LogP:	5.447 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.548 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.452 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	4.0
TPSA:	40.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	2.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.203	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.599	Fsp³:	0.667
MCE-18:	2.0 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.573	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? 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:	0.73	Promiscuous compounds:	0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.031	MDCK Permeability:	-4.621
Pgp-inhibitor:	0.0	Pgp-substrate:	0.0
PAMPA:	0.009 ? 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):	0.625
20% Bioavailability (F20%):	0.124	30% Bioavailability (F30%):	0.898
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.0
Plasma Protein Binding (PPB):	99.164%	Volume Distribution (VD):	0.406
Fu:	0.206% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.319
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.94
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.064	CYP2C19-substrate:	0.086
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.506
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.081	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.956 ? 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):

4.248

Half-life (T1/2):

0.903

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.586
Human Hepatotoxicity (H-HT):	0.82	Drug-induced Liver Injury (DILI):	0.041
AMES Toxicity:	0.041	Rat Oral Acute Toxicity:	0.582
Maximum Recommended Daily Dose:	0.372	Skin Sensitization:	0.604
Carcinogencity:	0.039	Eye Corrosion:	0.0
Eye Irritation:	0.605	Respiratory Toxicity:	1.0
Drug-induced Neurotoxicity:	0.079	Ototoxicity:	0.793
Hematotoxicity:	0.01	Drug-induced Nephrotoxicity:	0.787
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.233
A549 Cytotoxicity:	0.049	Hek293 Cytotoxicity:	0.13
BCF:	0.942 ? 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:	5.149 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.026 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.357 ? 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
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	red sea	n.a.	PMID[12762806]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[18027906]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22469701]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	collected by hand at a depth of 10 m off the shore of Iriomote Island, Okinawa Prefecture, Japan	2009-JUN	PMID[23855338]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[24948562]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[27015002]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	n.a.	New Guinea	n.a.	PMID[8158156]
NPO33070	Callyspongia sp.	Species	n.a.	n.a.	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	1

Activity Type	# Activity
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	370.0	nM	PMID[23855338]

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 NPC471281 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	40302
0.1-0.2	8705
0.2-0.3	673
0.3-0.4	83
0.4-0.5	31
0.5-0.6	30
0.6-0.7	8
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	1
0.95-1	11

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC125122
1.0	High Similarity	NPC471276
1.0	High Similarity	NPC471280
0.9524	High Similarity	NPC170776
0.9524	High Similarity	NPC9273
0.9524	High Similarity	NPC165447
0.9524	High Similarity	NPC471959
0.9524	High Similarity	NPC199286
0.9524	High Similarity	NPC489046
0.9524	High Similarity	NPC76198
0.9524	High Similarity	NPC610719
0.9091	High Similarity	NPC607242
0.8696	High Similarity	NPC249670
0.8333	Intermediate Similarity	NPC474642
0.8333	Intermediate Similarity	NPC473913
0.7692	Intermediate Similarity	NPC474644
0.6897	Remote Similarity	NPC471239
0.6897	Remote Similarity	NPC161838
0.6897	Remote Similarity	NPC474643
0.6897	Remote Similarity	NPC473865
0.6897	Remote Similarity	NPC55383
0.6667	Remote Similarity	NPC471960
0.6667	Remote Similarity	NPC477727
0.6061	Remote Similarity	NPC197272
0.5882	Remote Similarity	NPC89824
0.5882	Remote Similarity	NPC475477
0.5882	Remote Similarity	NPC256656
0.5882	Remote Similarity	NPC294278
0.5882	Remote Similarity	NPC477723
0.5714	Remote Similarity	NPC471278
0.5714	Remote Similarity	NPC470966
0.5667	Remote Similarity	NPC124183
0.5667	Remote Similarity	NPC482802
0.5556	Remote Similarity	NPC48058
0.5556	Remote Similarity	NPC470963
0.5556	Remote Similarity	NPC477661
0.5556	Remote Similarity	NPC603233
0.5556	Remote Similarity	NPC607245
0.5484	Remote Similarity	NPC91226
0.5484	Remote Similarity	NPC243546
0.5484	Remote Similarity	NPC31194
0.5484	Remote Similarity	NPC248884
0.5405	Remote Similarity	NPC470970
0.5312	Remote Similarity	NPC72699
0.5263	Remote Similarity	NPC224148
0.5263	Remote Similarity	NPC477726
0.5263	Remote Similarity	NPC477725
0.5152	Remote Similarity	NPC153538
0.5152	Remote Similarity	NPC93639
0.5128	Remote Similarity	NPC473896
0.5128	Remote Similarity	NPC473735
0.5128	Remote Similarity	NPC470969
0.5128	Remote Similarity	NPC146551
0.5128	Remote Similarity	NPC329608

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471281 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8403
0.1-0.2	708
0.2-0.3	36
0.3-0.4	2
0.4-0.5	1
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