NPASS Compound

Natural Product: NPC95899

Natural Product ID	NPC95899
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Flabelliferin B
IUPAC Name	[(4aS,4bR,6S,6aR,9S,10aS,10bR,12aS)-8-acetyl-9-hydroxy-1,1,4a,6a,10b-pentamethyl-2,3,4,4b,5,6,9,10,10a,11,12,12a-dodecahydrochrysen-6-yl] acetate
Synonyms	Flabelliferin B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2087231
PubChem CID	66554038
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001093] Carboxylic acid derivatives [CHEMONTID:0001238] Carboxylic acid esters

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 73 76 0 0 0 0 0 0 0 0999 V2000 2.2824 3.8588 -1.4893 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3203 3.0883 -0.2060 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9568 3.5159 0.7919 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6553 1.8751 -0.0709 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6513 1.1085 1.0973 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2200 0.9584 1.5932 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5526 0.2240 0.5457 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0681 -1.1948 0.4221 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3568 -1.0691 -0.0382 C 0 0 1 0 0 0 0 0 0 0 0 0 2.2527 -0.2674 0.8517 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4993 -0.8768 2.2076 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5676 -0.1715 0.2076 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9934 -0.8862 -0.7986 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3601 -0.6698 -1.3421 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7400 -1.3604 -2.2971 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2464 0.3470 -0.7556 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1207 -1.9109 -1.4105 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0394 -2.3253 -0.4455 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8421 -2.9983 -1.8940 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2843 -2.0656 1.5930 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8217 -1.8339 -0.7564 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3258 -1.7105 -0.5648 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6452 -0.2349 -0.5832 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0427 0.4016 0.6313 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5886 -0.0838 1.9288 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2657 1.9194 0.6007 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5056 2.3500 -0.0590 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5695 1.3423 -0.2543 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0833 0.0337 -0.8176 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0065 -1.0479 -0.2673 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3085 0.0006 -2.3396 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3948 3.5837 -2.0860 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2303 3.7758 -2.0442 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1897 4.9390 -1.2002 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2408 1.5685 1.9234 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1553 0.5378 2.5922 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1642 2.0191 1.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2610 0.7117 -0.4373 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2713 -0.4415 -0.9829 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4180 -0.3402 2.6030 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8403 -1.9408 2.1534 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7307 -0.6882 2.9557 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2574 0.5815 0.6211 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2877 0.2582 -1.0535 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2347 0.1666 0.3603 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8373 1.3716 -0.8743 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5774 -1.3865 -2.2520 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4004 -3.0544 -0.9771 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5304 -2.8804 0.3729 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9785 -2.8184 -2.8789 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1114 -2.8197 1.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4406 -1.5968 2.5561 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6260 -2.7263 1.7042 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6233 -2.9316 -0.8007 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5747 -1.3216 -1.7093 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7054 -2.2448 0.3004 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7673 -2.1306 -1.5093 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0660 0.1816 -1.4623 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8940 0.2992 2.7340 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7333 -1.1550 2.0237 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5718 0.3935 2.1927 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2110 2.2905 1.6613 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4016 2.4376 0.0927 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9514 3.1929 0.5481 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3063 2.8326 -1.0611 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2937 1.7636 -1.0154 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2266 1.1870 0.6524 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9871 -0.5938 0.0609 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2654 -1.8022 -1.0389 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6083 -1.5725 0.5916 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3417 1.0443 -2.7117 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2486 -0.4787 -2.6065 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4832 -0.5287 -2.8512 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 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 1 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 13 17 1 0 17 18 1 0 17 19 1 0 8 20 1 1 8 21 1 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 27 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 10 5 1 0 29 23 1 0 24 7 1 0 18 9 1 0 1 32 1 0 1 33 1 0 1 34 1 0 5 35 1 1 6 36 1 0 6 37 1 0 7 38 1 6 9 39 1 6 11 40 1 0 11 41 1 0 11 42 1 0 12 43 1 0 16 44 1 0 16 45 1 0 16 46 1 0 17 47 1 6 18 48 1 0 18 49 1 0 19 50 1 0 20 51 1 0 20 52 1 0 20 53 1 0 21 54 1 0 21 55 1 0 22 56 1 0 22 57 1 0 23 58 1 6 25 59 1 0 25 60 1 0 25 61 1 0 26 62 1 0 26 63 1 0 27 64 1 0 27 65 1 0 28 66 1 0 28 67 1 0 30 68 1 0 30 69 1 0 30 70 1 0 31 71 1 0 31 72 1 0 31 73 1 0 M END

Standard InCHIKey	JBPWKIMADBDSID-QGERINELSA-N
Standard InCHI	InChI=1S/C27H42O4/c1-16(28)18-15-27(7)21(13-19(18)30)26(6)12-9-20-24(3,4)10-8-11-25(20,5)22(26)14-23(27)31-17(2)29/h15,19-23,30H,8-14H2,1-7H3/t19-,20-,21-,22+,23-,25-,26-,27+/m0/s1
SMILES	CC(=O)O[C@H]1C[C@H]2[C@@]([C@H]3[C@@]1(C)C=C(C(=O)C)[C@H](C3)O)(C)CC[C@@H]1[C@]2(C)CCCC1(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	430.31	Volume:	468.574 ? Van der Waals volume.
Dense:	0.918	LogP:	3.647 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.567 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.367 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	23.0
TPSA:	63.6 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.59	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.856	Fsp³:	0.852
MCE-18:	84.48 ? 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:	0.65	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.309	Promiscuous compounds:	0.441

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.015	MDCK Permeability:	-4.747
Pgp-inhibitor:	0.993	Pgp-substrate:	0.001
PAMPA:	0.129 ? 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):	0.001
20% Bioavailability (F20%):	0.087	30% Bioavailability (F30%):	0.196
50% Bioavailability (F50%):	0.886

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.017	MRP1:	0.753
Plasma Protein Binding (PPB):	95.963%	Volume Distribution (VD):	-0.113
Fu:	5.55% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.096
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.062	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.664	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.997	CYP3A4-substrate:	0.957
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.182
HLM stability:	0.007 ? 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):

8.347

Half-life (T1/2):

0.643

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.273
Human Hepatotoxicity (H-HT):	0.482	Drug-induced Liver Injury (DILI):	0.499
AMES Toxicity:	0.484	Rat Oral Acute Toxicity:	0.701
Maximum Recommended Daily Dose:	0.908	Skin Sensitization:	0.949
Carcinogencity:	0.902	Eye Corrosion:	0.022
Eye Irritation:	0.717	Respiratory Toxicity:	0.921
Drug-induced Neurotoxicity:	0.176	Ototoxicity:	0.378
Hematotoxicity:	0.637	Drug-induced Nephrotoxicity:	0.939
Genotoxicity:	0.708	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.533	Hek293 Cytotoxicity:	0.434
BCF:	2.161 ? 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:	4.789 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.196 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.856 ? 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
NPO6368	Carteriospongia flabellifera	Species	Thorectidae	Eukaryota	n.a.	South Pacific	n.a.	PMID[22834941]
NPO6368	Carteriospongia flabellifera	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6368	Carteriospongia flabellifera	Species	Thorectidae	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
IC50	4

Activity Type	# Activity
Cell line	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
NPT386	Cell line	KM12	Homo sapiens	IC50	<	10000.0	nM	PMID[10869203]
NPT407	Cell line	COLO 205	Homo sapiens	IC50	<	10000.0	nM	PMID[10869203]
NPT386	Cell line	KM12	Homo sapiens	IC50	=	18000.0	nM	PMID[10869203]
NPT407	Cell line	COLO 205	Homo sapiens	IC50	=	20000.0	nM	PMID[16137881]

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 NPC95899 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	15406
0.1-0.2	25421
0.2-0.3	8408
0.3-0.4	512
0.4-0.5	81
0.5-0.6	17
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	Natural Product ID
0.7759	Intermediate Similarity	NPC489145
0.75	Intermediate Similarity	NPC489146
0.7458	Intermediate Similarity	NPC489144
0.7213	Intermediate Similarity	NPC489000
0.7143	Intermediate Similarity	NPC489148
0.7143	Intermediate Similarity	NPC489147
0.7097	Intermediate Similarity	NPC488999
0.6721	Remote Similarity	NPC325229
0.6032	Remote Similarity	NPC608115
0.6032	Remote Similarity	NPC611248
0.6	Remote Similarity	NPC83242
0.5938	Remote Similarity	NPC606805
0.5938	Remote Similarity	NPC607360
0.5902	Remote Similarity	NPC219535
0.5714	Remote Similarity	NPC131104
0.5645	Remote Similarity	NPC602574
0.5556	Remote Similarity	NPC601034
0.5312	Remote Similarity	NPC269729
0.5312	Remote Similarity	NPC606340
0.5303	Remote Similarity	NPC208912
0.5303	Remote Similarity	NPC194951
0.5231	Remote Similarity	NPC275086
0.5224	Remote Similarity	NPC51499
0.5156	Remote Similarity	NPC328141
0.5072	Remote Similarity	NPC474253
0.5072	Remote Similarity	NPC228251
0.5072	Remote Similarity	NPC474346
0.5072	Remote Similarity	NPC477972

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC95899 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6346
0.1-0.2	2621
0.2-0.3	182
0.3-0.4	1
0.4-0.5	0
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