NPASS Compound

Natural Product: NPC605339

Natural Product ID	NPC605339
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PTHKHRXTRBUUGO-JMHCWUSJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL354262
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 57 59 0 0 0 0 0 0 0 0999 V2000 2.7538 -1.8032 -2.0486 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2081 -1.7426 -0.8772 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3332 -2.6792 0.2147 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9851 -3.7472 0.2822 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5646 -2.2151 1.3079 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5878 -1.3106 0.8058 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3076 -0.6713 -0.3764 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0381 0.5289 0.0968 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3000 0.2225 0.6731 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6407 0.3847 1.9865 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9762 0.0504 2.5485 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7253 0.8549 2.7403 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1008 1.6667 -0.8537 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8549 2.3838 -1.1565 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9534 3.5140 -2.1471 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2947 2.0670 -0.6000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5714 2.7734 -0.8825 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6486 1.9653 -1.4883 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9720 0.7011 -0.7162 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3515 0.9372 0.6991 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9040 -0.4355 -1.3515 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1303 -1.8080 -0.9525 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1024 -2.2156 0.4559 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7093 -2.1042 1.0782 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7094 -1.7720 2.5398 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9007 -3.3114 0.8724 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6203 -2.0320 0.2756 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5938 -1.0321 -2.8160 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4060 -2.6488 -2.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3656 -0.5297 1.5451 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5867 -0.4186 -1.1451 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4478 0.9179 0.9889 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9629 -0.8290 3.2044 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6366 -0.1721 1.6730 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4368 0.9496 3.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8151 2.4681 -0.4933 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5930 1.3187 -1.8064 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0216 3.6726 -2.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5445 4.4568 -1.7296 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4645 3.2429 -3.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3536 1.2566 0.1324 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9622 3.2257 0.0637 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3197 3.6778 -1.5109 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5875 2.5610 -1.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4867 1.7412 -2.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3317 0.4823 0.9698 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5353 0.7155 1.4134 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5471 2.0419 0.8888 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6139 -0.3721 -2.4458 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4383 -2.5064 -1.5162 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1390 -2.1028 -1.4025 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8090 -1.7931 1.1521 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3202 -3.3270 0.4676 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2470 -2.5512 3.1912 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7741 -1.6938 2.8970 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2366 -0.7808 2.7413 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5878 -2.1735 -0.8313 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 3 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 10 12 2 0 8 13 1 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 1 24 26 1 0 26 27 1 0 7 2 1 0 27 24 1 0 27 6 1 0 1 28 1 0 1 29 1 0 6 30 1 1 7 31 1 6 8 32 1 1 11 33 1 0 11 34 1 0 11 35 1 0 13 36 1 0 13 37 1 0 15 38 1 0 15 39 1 0 15 40 1 0 16 41 1 0 17 42 1 0 17 43 1 0 18 44 1 0 18 45 1 0 20 46 1 0 20 47 1 0 20 48 1 0 21 49 1 0 22 50 1 0 22 51 1 0 23 52 1 0 23 53 1 0 25 54 1 0 25 55 1 0 25 56 1 0 27 57 1 6 M END

Standard InCHIKey	PTHKHRXTRBUUGO-JMHCWUSJSA-N
Standard InCHI	InChI=1S/C22H30O5/c1-13-8-6-9-14(2)12-17(25-16(4)23)18-15(3)21(24)26-19(18)20-22(5,27-20)11-7-10-13/h9-10,17-20H,3,6-8,11-12H2,1-2,4-5H3/b13-10+,14-9+/t17-,18+,19-,20+,22+/m0/s1
SMILES	C=C1C(=O)O[C@H]2[C@H]1[C@@H](OC(C)=O)C/C(C)=C/CC/C(C)=C/CC[C@@]1(C)O[C@H]21

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.21	Volume:	394.168 ? Van der Waals volume.
Dense:	0.949	LogP:	3.316 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.182 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.906 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	23.0
TPSA:	65.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.3	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.944	Fsp³:	0.636
MCE-18:	53.667 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.477	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.029 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.491	Promiscuous compounds:	0.352

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.78	MDCK Permeability:	-4.817
Pgp-inhibitor:	0.999	Pgp-substrate:	0.003
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):	0.002
20% Bioavailability (F20%):	0.029	30% Bioavailability (F30%):	0.533
50% Bioavailability (F50%):	0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.909
Plasma Protein Binding (PPB):	82.532%	Volume Distribution (VD):	-0.064
Fu:	13.748% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.005
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.097	CYP1A2-substrate:	0.311
CYP2C19-inhibitor:	0.368	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.038	CYP2C9-substrate:	0.018
CYP2D6-inhibitor:	0.03	CYP2D6-substrate:	0.023
CYP3A4-inhibitor:	0.008	CYP3A4-substrate:	0.917
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.989
HLM stability:	0.937 ? 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):

9.062

Half-life (T1/2):

1.052

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.07
Human Hepatotoxicity (H-HT):	0.497	Drug-induced Liver Injury (DILI):	0.784
AMES Toxicity:	0.214	Rat Oral Acute Toxicity:	0.073
Maximum Recommended Daily Dose:	0.108	Skin Sensitization:	0.987
Carcinogencity:	0.198	Eye Corrosion:	0.262
Eye Irritation:	0.969	Respiratory Toxicity:	0.016
Drug-induced Neurotoxicity:	0.106	Ototoxicity:	0.288
Hematotoxicity:	0.287	Drug-induced Nephrotoxicity:	0.441
Genotoxicity:	0.051	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.033	Hek293 Cytotoxicity:	0.168
BCF:	1.602 ? 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:	4.385 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.278 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.747 ? 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
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	south china sea	n.a.	PMID[18512986]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18973388]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548852]
NPO27251	Lobophytum crassum	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27251	Lobophytum crassum	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
Ki	1
IC50	2
Inhibition	1

Activity Type	# Activity
Protein complex	4

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
NPT29071	Protein complex	Geranylgeranyl transferase type I	Homo sapiens	IC50	=	5300.0	nM	DOI[10.1016/0960-894X(96)00142-4]
NPT29670	Protein complex	Protein farnesyltransferase	Homo sapiens	Ki	=	170.0	nM	DOI[10.1016/0960-894X(96)00142-4]
NPT29670	Protein complex	Protein farnesyltransferase	Homo sapiens	IC50	=	150.0	nM	DOI[10.1016/0960-894X(96)00142-4]
NPT29670	Protein complex	Protein farnesyltransferase	Homo sapiens	Inhibition	=	26.0	%	DOI[10.1016/0960-894X(96)00142-4]

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 NPC605339 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	24040
0.1-0.2	22971
0.2-0.3	2419
0.3-0.4	338
0.4-0.5	57
0.5-0.6	17
0.6-0.7	12
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9149	High Similarity	NPC151770
0.7963	Intermediate Similarity	NPC483718
0.7069	Intermediate Similarity	NPC288876
0.6607	Remote Similarity	NPC481994
0.6491	Remote Similarity	NPC481908
0.6491	Remote Similarity	NPC481993
0.6296	Remote Similarity	NPC38468
0.6296	Remote Similarity	NPC192678
0.6296	Remote Similarity	NPC319795
0.6296	Remote Similarity	NPC50362
0.6296	Remote Similarity	NPC488056
0.6296	Remote Similarity	NPC605079
0.6226	Remote Similarity	NPC93213
0.6038	Remote Similarity	NPC171204
0.6038	Remote Similarity	NPC606745
0.5965	Remote Similarity	NPC5130
0.5862	Remote Similarity	NPC272814
0.5667	Remote Similarity	NPC481801
0.5593	Remote Similarity	NPC483976
0.5484	Remote Similarity	NPC485393
0.5397	Remote Similarity	NPC475748
0.5397	Remote Similarity	NPC264477
0.5357	Remote Similarity	NPC611318
0.5345	Remote Similarity	NPC49342
0.5345	Remote Similarity	NPC251385
0.5238	Remote Similarity	NPC231889
0.5238	Remote Similarity	NPC483935
0.5172	Remote Similarity	NPC256273
0.5167	Remote Similarity	NPC608845
0.5088	Remote Similarity	NPC207188
0.5079	Remote Similarity	NPC212486
0.5077	Remote Similarity	NPC481805

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC605339 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7441
0.1-0.2	1673
0.2-0.3	34
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
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
0.6296	Remote Similarity	NPD1733	Clinical (unspecified phase)

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