NPASS Compound

Natural Product: NPC573598

Natural Product ID	NPC573598
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-17-[(~{E},1~{R})-5-hydroxy-1,5-dimethyl-hex-2-enyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
IUPAC Name	(8~{S},9~{S},10~{R},13~{R},14~{S},17~{R})-17-[(~{E},1~{R})-5-hydroxy-1,5-dimethyl-hex-2-enyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
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 71 74 0 0 0 0 0 0 0 0999 V2000 1.9838 -1.1943 -2.3598 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2325 0.1112 -1.5739 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6534 0.3675 -1.4610 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3910 0.6009 -0.4110 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8902 0.8483 -0.5409 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5944 -0.2191 0.2559 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2071 -0.1792 1.7047 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2565 -1.5767 -0.2936 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9776 0.0430 0.1307 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3637 0.1179 -0.3917 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5467 1.3335 0.5072 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1685 1.8219 0.9207 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6209 0.5484 0.6768 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.0688 0.6761 0.8401 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.4235 0.5639 2.2917 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4865 -0.4030 2.6564 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5128 -0.6518 1.6352 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6323 -1.2562 1.9507 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6765 -1.5183 0.9452 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7339 -2.1389 1.2766 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4697 -1.0528 -0.4273 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0102 -1.0428 -0.7532 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2368 -0.2055 0.2444 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5762 1.2401 0.0884 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7426 -0.4422 0.0802 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3210 -0.4959 -1.3431 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8096 -0.8460 -1.3409 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1269 0.3123 -0.7481 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3228 1.5933 -1.5334 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0225 -1.6451 -2.4839 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4492 -1.9351 -1.7680 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5384 -1.0497 -3.3298 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7961 0.8936 -2.2871 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2342 0.3712 -2.4165 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9405 0.6072 0.5636 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1510 1.8648 -0.2237 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1952 0.7298 -1.5999 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6551 0.7342 1.9603 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6344 -1.0787 1.9991 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1438 -0.1965 2.3326 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1043 -2.2603 -0.0840 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3260 -1.9537 0.1792 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1016 -1.5908 -1.3849 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0890 1.0239 0.0572 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3866 -0.7929 0.2350 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9642 0.9464 1.4964 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1644 2.1185 0.0855 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1615 2.6814 0.3369 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1170 2.1178 1.9878 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1730 -0.2156 1.3712 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4171 1.6684 0.4762 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6704 1.5836 2.7087 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5183 0.2688 2.9086 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0527 0.0348 3.5369 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0818 -1.3575 3.0863 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8110 -1.5763 2.9645 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9690 -1.7682 -1.1183 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9801 -0.0793 -0.6093 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8366 -0.5985 -1.7506 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6578 -2.0881 -0.7711 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3739 1.7948 1.0350 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0280 1.7159 -0.7716 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6517 1.3849 -0.1297 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4854 -1.4048 0.5647 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8364 -1.3240 -1.8433 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4682 0.4746 -1.8437 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5207 -1.0004 -2.4062 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6788 -1.7385 -0.7335 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4403 1.3207 -2.6142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2636 2.1181 -1.2744 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5685 2.2450 -1.4695 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 6 8 1 0 6 9 1 0 2 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 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 1 23 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 6 28 10 1 0 28 13 1 0 25 14 1 0 23 17 1 0 1 30 1 0 1 31 1 0 1 32 1 0 2 33 1 6 3 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 7 38 1 0 7 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 10 45 1 1 11 46 1 0 11 47 1 0 12 48 1 0 12 49 1 0 13 50 1 1 14 51 1 6 15 52 1 0 15 53 1 0 16 54 1 0 16 55 1 0 18 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 22 60 1 0 24 61 1 0 24 62 1 0 24 63 1 0 25 64 1 1 26 65 1 0 26 66 1 0 27 67 1 0 27 68 1 0 29 69 1 0 29 70 1 0 29 71 1 0 M END

Standard InCHIKey	PPTZQYHPGFMZNH-LNFKEUGRSA-N
Standard InCHI	InChI=1S/C27H42O2/c1-18(7-6-14-25(2,3)29)22-10-11-23-21-9-8-19-17-20(28)12-15-26(19,4)24(21)13-16-27(22,23)5/h6-7,17-18,21-24,29H,8-16H2,1-5H3/b7-6+/t18-,21+,22-,23+,24+,26+,27-/m1/s1
SMILES	C[C@H](/C=C/CC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	398.32	Volume:	450.993 ? Van der Waals volume.
Dense:	0.883	LogP:	4.938 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.039 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.818 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.55	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.45	Fsp³:	0.815
MCE-18:	72.0 ? 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:	0.725	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? 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:	0.563	Promiscuous compounds:	0.483

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.986	MDCK Permeability:	-4.776
Pgp-inhibitor:	0.973	Pgp-substrate:	0.0
PAMPA:	0.0 ? 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%):	0.006	30% Bioavailability (F30%):	0.039
50% Bioavailability (F50%):	0.6

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.096	MRP1:	0.03
Plasma Protein Binding (PPB):	97.33%	Volume Distribution (VD):	-0.011
Fu:	2.721% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.505
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.086
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.125
CYP2D6-inhibitor:	0.076	CYP2D6-substrate:	0.653
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.987 ? 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):

2.706

Half-life (T1/2):

0.712

ADMET: Toxicity

hERG Blockers:	0.118	hERG Blockers (10um):	0.244
Human Hepatotoxicity (H-HT):	0.885	Drug-induced Liver Injury (DILI):	0.388
AMES Toxicity:	0.195	Rat Oral Acute Toxicity:	0.073
Maximum Recommended Daily Dose:	0.441	Skin Sensitization:	0.945
Carcinogencity:	0.959	Eye Corrosion:	0.015
Eye Irritation:	0.805	Respiratory Toxicity:	0.787
Drug-induced Neurotoxicity:	0.163	Ototoxicity:	0.661
Hematotoxicity:	0.823	Drug-induced Nephrotoxicity:	0.663
Genotoxicity:	0.491	RPMI-8226 Immunitoxicity:	0.055
A549 Cytotoxicity:	0.033	Hek293 Cytotoxicity:	0.688
BCF:	1.924 ? 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:	4.114 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.439 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.949 ? 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
NPO25775	Dasystenella acanthina	Species	Primnoidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25775	Dasystenella acanthina	Species	Primnoidae	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

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

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 NPC573598 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	14708
0.1-0.2	29545
0.2-0.3	5305
0.3-0.4	222
0.4-0.5	46
0.5-0.6	19
0.6-0.7	12
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	Natural Product ID
0.75	Intermediate Similarity	NPC115023
0.6981	Remote Similarity	NPC214043
0.6981	Remote Similarity	NPC85774
0.6731	Remote Similarity	NPC307176
0.6731	Remote Similarity	NPC321874
0.6727	Remote Similarity	NPC237712
0.6667	Remote Similarity	NPC282593
0.6545	Remote Similarity	NPC35734
0.6545	Remote Similarity	NPC159577
0.6545	Remote Similarity	NPC602429
0.6429	Remote Similarity	NPC149203
0.6316	Remote Similarity	NPC249312
0.625	Remote Similarity	NPC144258
0.5932	Remote Similarity	NPC310010
0.5932	Remote Similarity	NPC326627
0.5806	Remote Similarity	NPC320514
0.5789	Remote Similarity	NPC227064
0.5789	Remote Similarity	NPC329043
0.5789	Remote Similarity	NPC58841
0.5789	Remote Similarity	NPC161423
0.569	Remote Similarity	NPC327115
0.5636	Remote Similarity	NPC139397
0.5439	Remote Similarity	NPC2634
0.5439	Remote Similarity	NPC265782
0.5439	Remote Similarity	NPC251929
0.5333	Remote Similarity	NPC328539
0.5323	Remote Similarity	NPC469948
0.5246	Remote Similarity	NPC176107
0.5246	Remote Similarity	NPC323765
0.5156	Remote Similarity	NPC309603
0.5079	Remote Similarity	NPC185936
0.5079	Remote Similarity	NPC168027

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC573598 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5823
0.1-0.2	3010
0.2-0.3	206
0.3-0.4	69
0.4-0.5	28
0.5-0.6	9
0.6-0.7	4
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
0.6731	Remote Similarity	NPD4747	Phase 4
0.6364	Remote Similarity	NPD4221	Phase 4
0.6102	Remote Similarity	NPD5737	Phase 4
0.6034	Remote Similarity	NPD4693	Phase 3
0.5932	Remote Similarity	NPD4753	Phase 2
0.5902	Remote Similarity	NPD6672	Phase 4
0.5789	Remote Similarity	NPD3666	Phase 4
0.5439	Remote Similarity	NPD4691	Approved
0.5231	Remote Similarity	NPD6083	Phase 4
0.5231	Remote Similarity	NPD6084	Phase 2
0.5161	Remote Similarity	NPD5330	Phase 4
0.5161	Remote Similarity	NPD6938	Clinical (unspecified phase)
0.5161	Remote Similarity	NPD6939	Phase 3

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