NPASS Compound

Natural Product: NPC176107

Natural Product ID	NPC176107
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Dendronesterone C
IUPAC Name	(8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(E,2R)-6-methylhept-3-en-2-yl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one
Synonyms	Dendronesterone C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL457600
PubChem CID	11176468
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0003566] Cholestane steroids [CHEMONTID:0001469] Cholesterols 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 68 71 0 0 0 0 0 0 0 0999 V2000 7.5265 -1.0672 0.4429 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0983 -0.8625 0.0263 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4260 0.1209 0.9712 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9873 0.3248 0.5484 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5877 1.5274 0.2214 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2092 1.8606 -0.2066 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3091 0.7145 0.0043 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3199 0.3849 1.5034 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1204 0.7135 1.9713 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8099 0.1310 0.7891 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1404 0.9087 -0.3556 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5882 2.3200 -0.3884 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5414 0.0860 -1.5680 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0151 -0.0595 -1.6827 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6834 -0.6412 -0.4756 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2822 0.2475 0.7150 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9826 -0.0671 1.9864 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4853 0.1720 1.7719 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8393 -0.8147 0.6851 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7339 -1.7125 0.9503 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1606 -2.7340 -0.0149 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0153 -3.5929 0.2303 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5133 -2.6878 -1.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6081 -1.7500 -1.5336 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1717 -0.7198 -0.6089 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7106 0.6014 -1.2301 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3432 2.3756 -1.6192 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3769 -2.1925 0.0560 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6892 -0.5984 1.4344 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7421 -2.1400 0.5626 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2454 -0.6485 -0.3105 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0949 -0.4584 -0.9934 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4861 -0.2490 2.0141 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9969 1.0696 0.9087 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3739 -0.5611 0.5294 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3511 2.3318 0.2769 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9288 2.7319 0.4895 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7449 -0.1517 -0.5825 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4055 -0.7308 1.6439 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0794 0.8890 2.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3475 0.1506 2.8934 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2623 1.7718 2.1501 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5039 -0.9149 0.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3210 2.5144 -1.2047 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2596 2.9889 -0.6037 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1314 2.6390 0.5369 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1537 0.4441 -2.5157 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1139 -0.9297 -1.3924 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4325 0.9237 -1.9822 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2079 -0.7275 -2.5691 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2432 -1.6285 -0.2835 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5871 1.2685 0.4096 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8938 -1.1397 2.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5941 0.5832 2.7668 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0121 -0.0098 2.7000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6135 1.1698 1.3442 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2141 -1.7322 1.9436 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7582 -3.4129 -2.1051 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1558 -1.7991 -2.5698 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7016 0.5164 -2.3354 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7537 0.7752 -0.8927 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1149 1.4558 -0.9242 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3786 3.4841 -1.5743 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5891 2.0442 -2.3209 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3417 2.0993 -2.0798 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2933 -2.5643 1.0920 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9789 -2.9221 -0.5295 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3545 -2.1196 -0.3677 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 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 6 11 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 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 1 6 6 27 1 0 2 28 1 0 11 7 1 0 25 15 1 0 16 10 1 0 25 19 1 0 1 29 1 0 1 30 1 0 1 31 1 0 2 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 5 36 1 0 6 37 1 1 7 38 1 6 8 39 1 0 8 40 1 0 9 41 1 0 9 42 1 0 10 43 1 6 12 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 1 16 52 1 6 17 53 1 0 17 54 1 0 18 55 1 0 18 56 1 0 20 57 1 0 23 58 1 0 24 59 1 0 26 60 1 0 26 61 1 0 26 62 1 0 27 63 1 0 27 64 1 0 27 65 1 0 28 66 1 0 28 67 1 0 28 68 1 0 M END

Standard InCHIKey	AJWONNNXQUONDT-UAJHHUEASA-N
Standard InCHI	InChI=1S/C27H40O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h6,8,13,15,17-19,22-25H,7,9-12,14,16H2,1-5H3/b8-6+/t19-,22+,23-,24+,25+,26+,27-/m1/s1
SMILES	CC(C/C=C/[C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]1[C@H]2CCC2=CC(=O)C=C[C@]12C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	380.31	Volume:	439.567 ? Van der Waals volume.
Dense:	0.865	LogP:	6.022 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.322 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.047 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	22.0
TPSA:	17.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.473	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.42	Fsp³:	0.741
MCE-18:	65.277 ? 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:	0.959	Fluc inhibitor:	0.312 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.036 ? 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:	0.714	Promiscuous compounds:	0.146

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.136	MDCK Permeability:	-4.851
Pgp-inhibitor:	0.998	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%):	0.05	30% Bioavailability (F30%):	0.548
50% Bioavailability (F50%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.033
Plasma Protein Binding (PPB):	98.818%	Volume Distribution (VD):	0.467
Fu:	1.008% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.049
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.968
CYP2C19-inhibitor:	0.169	CYP2C19-substrate:	0.036
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.642
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

11.614

Half-life (T1/2):

0.241

ADMET: Toxicity

hERG Blockers:	0.233	hERG Blockers (10um):	0.577
Human Hepatotoxicity (H-HT):	0.84	Drug-induced Liver Injury (DILI):	0.183
AMES Toxicity:	0.068	Rat Oral Acute Toxicity:	0.335
Maximum Recommended Daily Dose:	0.94	Skin Sensitization:	0.962
Carcinogencity:	0.9	Eye Corrosion:	0.34
Eye Irritation:	0.991	Respiratory Toxicity:	0.976
Drug-induced Neurotoxicity:	0.213	Ototoxicity:	0.461
Hematotoxicity:	0.41	Drug-induced Nephrotoxicity:	0.301
Genotoxicity:	0.563	RPMI-8226 Immunitoxicity:	0.069
A549 Cytotoxicity:	0.053	Hek293 Cytotoxicity:	0.684
BCF:	3.218 ? 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:	4.952 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.891 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.922 ? 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
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10843584]
NPO33357	lemnalia carvicorni	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497934]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15497934]
NPO14183	Dendronephthya studeri	Species	Nephtheidae	Eukaryota	n.a.	at a depth of 20 m, the coast of Xiaodong Sea, Hainan Province, China	2001-DEC	PMID[21192715]
NPO14183	Dendronephthya studeri	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21192715]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[30407007]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25976	Dendronephthya gigantea	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14183	Dendronephthya studeri	Species	Nephtheidae	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

Activity Type	# Activity
Cell line	2

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	>	100.0	uM	PMID[15497934]
NPT168	Cell line	P388	Mus musculus	ED50	>	100.0	uM	PMID[15497934]

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 NPC176107 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	21823
0.1-0.2	25740
0.2-0.3	2150
0.3-0.4	97
0.4-0.5	25
0.5-0.6	12
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	0

Similarity Score	Similarity Level	Natural Product ID
0.7551	Intermediate Similarity	NPC92327
0.7547	Intermediate Similarity	NPC105197
0.7273	Intermediate Similarity	NPC474463
0.6066	Remote Similarity	NPC190211
0.6066	Remote Similarity	NPC218301
0.6066	Remote Similarity	NPC273199
0.5968	Remote Similarity	NPC608739
0.5873	Remote Similarity	NPC255309
0.5818	Remote Similarity	NPC54123
0.5606	Remote Similarity	NPC177141
0.5517	Remote Similarity	NPC6434
0.5385	Remote Similarity	NPC470923
0.5254	Remote Similarity	NPC234707
0.5224	Remote Similarity	NPC164835
0.5224	Remote Similarity	NPC228669
0.5147	Remote Similarity	NPC128488
0.5147	Remote Similarity	NPC304968
0.5075	Remote Similarity	NPC310981

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC176107 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7041
0.1-0.2	1837
0.2-0.3	213
0.3-0.4	48
0.4-0.5	9
0.5-0.6	1
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
0.5789	Remote Similarity	NPD4195	Phase 4

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