NPASS Compound

Natural Product: NPC329986

Natural Product ID	NPC329986
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Boivinide C
IUPAC Name	(3S,5S,8R,9S,10R,13R,14S,17S)-14-hydroxy-3-[(2R,4S,5S,6R)-4-methoxy-6-methyl-5-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-13-methyl-17-(5-oxo-2H-furan-3-yl)-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-10-carbaldehyde
Synonyms	boivinide C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL251691
PubChem CID	44445750
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 103109 0 0 0 0 0 0 0 0999 V2000 -4.4843 3.4076 -0.0440 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9327 2.1544 0.2149 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4683 1.1744 -0.6191 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3210 0.5241 -1.3531 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4171 -0.0603 -0.2599 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2206 -0.4763 -0.7729 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1187 0.1589 -0.2084 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7665 -0.7635 0.5481 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9398 -1.2181 -0.2555 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7756 -0.1336 -0.8385 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0330 1.1855 -0.6216 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6364 1.0121 -1.1657 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7960 2.3188 -1.2303 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0904 2.4273 -0.4096 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8477 1.1572 -0.5915 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0947 -0.0641 -0.1116 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9375 -1.2618 -0.5333 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3307 -1.1686 0.0440 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0763 0.0655 -0.3515 C 0 0 1 0 0 0 0 0 0 0 0 0 6.2206 1.2748 -0.0089 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7786 2.4637 -0.4735 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2500 1.2798 1.4806 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5926 0.6536 1.8561 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2392 0.2553 0.5673 C 0 0 1 0 0 0 0 0 0 0 0 0 9.1140 -0.9446 0.6987 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4069 -1.6391 1.7662 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2911 -2.7128 1.4215 C 0 0 0 0 0 0 0 0 0 0 0 0 10.8100 -3.6097 2.1482 O 0 0 0 0 0 0 0 0 0 0 0 0 10.5223 -2.6318 0.0725 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8127 -1.5480 -0.4490 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4708 0.0712 -1.8091 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9601 -0.4171 -2.2905 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4596 -1.4142 -2.8235 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1055 -1.1701 0.2259 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1885 -0.7429 0.9665 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1473 0.1413 0.2441 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1455 -0.5367 -0.4535 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4113 -0.2435 0.0273 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.0466 -1.3740 0.5015 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3194 -0.9473 0.9440 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.7979 -1.9204 1.9813 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9297 -1.9695 3.0579 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.2105 -0.8789 -0.2516 C 0 0 2 0 0 0 0 0 0 0 0 0 -9.3416 -0.5670 -1.4593 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.2141 0.3920 -1.0863 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.7131 1.6397 -0.7085 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7211 -1.7520 -1.8881 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.1719 0.1261 -0.1500 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9500 -1.9540 1.4830 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5716 3.4386 0.1002 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2571 3.6868 -1.0838 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0283 4.1030 0.7103 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2234 1.5897 -1.3170 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7557 1.2638 -1.9602 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7304 -0.3103 -1.9569 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3280 0.7203 0.5221 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5658 0.8717 0.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1790 -0.2045 1.4365 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2145 -1.6163 1.0138 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5317 -1.9030 -1.0531 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5583 -1.8857 0.3916 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0315 1.3581 0.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7466 0.5552 -2.1763 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1922 2.0316 -1.2252 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0378 2.0685 -2.2766 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2042 3.2464 -1.1283 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7675 2.5608 0.6580 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6876 3.2731 -0.7702 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9712 1.0101 -1.7020 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8795 -0.0682 0.9583 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4859 -2.1642 -0.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9144 -1.3094 -1.6284 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2182 -1.1851 1.1489 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8753 -2.0679 -0.2648 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7449 3.1817 0.2176 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2644 2.3345 1.8808 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4342 0.7590 1.9808 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3954 -0.2135 2.5296 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2413 1.3796 2.3831 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8630 1.0840 0.1593 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0280 -1.4210 2.7577 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4922 -0.8213 -0.9567 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0809 -1.9802 -1.1795 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5612 0.2226 -1.9403 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2249 -0.9172 -2.2476 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8736 0.8100 -2.3847 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5314 0.2158 -2.9611 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8222 -0.1851 1.8745 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6928 0.7402 1.0389 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3402 0.4812 0.8716 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2111 0.0440 1.4669 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.8423 -1.6864 2.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8219 -2.9655 1.5576 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9312 -1.1340 3.5989 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7079 -1.8504 -0.4276 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9623 -0.1069 -2.2470 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6097 0.5414 -2.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.0457 2.1167 -1.5016 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1183 -2.5374 -1.4036 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.0864 -0.2458 -0.3106 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6878 -1.5934 2.2227 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5082 -2.4008 0.6419 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2586 -2.6782 1.9606 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 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 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 1 0 20 21 1 6 20 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 19 31 1 6 10 32 1 6 32 33 2 0 5 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 40 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 44 47 1 0 43 48 1 0 35 49 1 0 36 3 1 0 45 38 1 0 12 7 1 0 20 15 1 0 30 25 1 0 16 10 1 0 24 19 1 0 1 50 1 0 1 51 1 0 1 52 1 0 3 53 1 6 4 54 1 0 4 55 1 0 5 56 1 1 7 57 1 1 8 58 1 0 8 59 1 0 9 60 1 0 9 61 1 0 11 62 1 1 12 63 1 0 12 64 1 0 13 65 1 0 13 66 1 0 14 67 1 0 14 68 1 0 15 69 1 6 16 70 1 1 17 71 1 0 17 72 1 0 18 73 1 0 18 74 1 0 21 75 1 0 22 76 1 0 22 77 1 0 23 78 1 0 23 79 1 0 24 80 1 6 26 81 1 0 30 82 1 0 30 83 1 0 31 84 1 0 31 85 1 0 31 86 1 0 32 87 1 0 35 88 1 1 36 89 1 1 38 90 1 1 40 91 1 1 41 92 1 0 41 93 1 0 42 94 1 0 43 95 1 6 44 96 1 6 45 97 1 6 46 98 1 0 47 99 1 0 48100 1 0 49101 1 0 49102 1 0 49103 1 0 M END

Standard InCHIKey	CSVNMGCNZRUZHN-CMVMYSFUSA-N
Standard InCHI	InChI=1S/C36H54O13/c1-18-32(49-33-31(42)30(41)29(40)26(15-37)48-33)25(44-3)14-28(46-18)47-21-6-10-35(17-38)20(13-21)4-5-24-23(35)7-9-34(2)22(8-11-36(24,34)43)19-12-27(39)45-16-19/h12,17-18,20-26,28-33,37,40-43H,4-11,13-16H2,1-3H3/t18-,20+,21+,22+,23+,24-,25+,26-,28+,29-,30+,31-,32+,33+,34-,35-,36+/m1/s1
SMILES	CO[C@H]1C[C@H](O[C@H]2CC[C@]3([C@H](C2)CC[C@@H]2[C@@H]3CC[C@]3([C@]2(O)CC[C@H]3C2=CC(=O)OC2)C)C=O)O[C@@H]([C@@H]1O[C@@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	694.36	Volume:	677.68 ? Van der Waals volume.
Dense:	1.025	LogP:	0.546 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.171 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.59 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	39.0
TPSA:	190.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	7.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.138	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.714	Fsp³:	0.889
MCE-18:	129.882 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.831	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.169	Promiscuous compounds:	0.172

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.743	MDCK Permeability:	-5.264
Pgp-inhibitor:	0.038	Pgp-substrate:	0.926
PAMPA:	0.785 ? 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):	0.008
20% Bioavailability (F20%):	0.639	30% Bioavailability (F30%):	0.926
50% Bioavailability (F50%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.512
Plasma Protein Binding (PPB):	65.423%	Volume Distribution (VD):	-0.324
Fu:	32.852% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.009
BSEP inhibitor:	0.855

ADMET: Metabolism

CYP1A2-inhibitor:	0.506	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.031	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.011
HLM stability:	0.147 ? 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):

1.591

Half-life (T1/2):

3.29

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.046
Human Hepatotoxicity (H-HT):	0.731	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.998	Rat Oral Acute Toxicity:	0.468
Maximum Recommended Daily Dose:	0.878	Skin Sensitization:	1.0
Carcinogencity:	0.908	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.077
Drug-induced Neurotoxicity:	0.024	Ototoxicity:	0.984
Hematotoxicity:	0.945	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.624
A549 Cytotoxicity:	0.974	Hek293 Cytotoxicity:	0.933
BCF:	0.527 ? 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:	3.33 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.056 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.184 ? 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
NPO33407	roupellina boivinii	Species	n.a.	n.a.	n.a.	Madagascar rainforest	n.a.	PMID[17988099]

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
Cell line	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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	2900.0	nM	PMID[12713412]

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 NPC329986 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	14293
0.1-0.2	30486
0.2-0.3	4383
0.3-0.4	460
0.4-0.5	86
0.5-0.6	66
0.6-0.7	53
0.7-0.8	0
0.8-0.85	6
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC140092
0.8523	High Similarity	NPC232785
0.8523	High Similarity	NPC486139
0.8313	Intermediate Similarity	NPC480914
0.8202	Intermediate Similarity	NPC125077
0.8132	Intermediate Similarity	NPC486138
0.8132	Intermediate Similarity	NPC276838
0.8085	Intermediate Similarity	NPC475419
0.8022	Intermediate Similarity	NPC146857
0.7778	Intermediate Similarity	NPC188234
0.7755	Intermediate Similarity	NPC474423
0.7551	Intermediate Similarity	NPC486150
0.7526	Intermediate Similarity	NPC74259
0.7449	Intermediate Similarity	NPC474908
0.7449	Intermediate Similarity	NPC329675
0.7449	Intermediate Similarity	NPC194716
0.7419	Intermediate Similarity	NPC486143
0.7419	Intermediate Similarity	NPC486135
0.7419	Intermediate Similarity	NPC486142
0.7419	Intermediate Similarity	NPC486137
0.7419	Intermediate Similarity	NPC486149
0.7356	Intermediate Similarity	NPC469750
0.7347	Intermediate Similarity	NPC120390
0.7159	Intermediate Similarity	NPC5311
0.7159	Intermediate Similarity	NPC77299
0.7159	Intermediate Similarity	NPC480906
0.7083	Intermediate Similarity	NPC486146
0.697	Remote Similarity	NPC486144
0.697	Remote Similarity	NPC486145
0.697	Remote Similarity	NPC486147
0.697	Remote Similarity	NPC486136
0.697	Remote Similarity	NPC486148
0.6863	Remote Similarity	NPC329784
0.6774	Remote Similarity	NPC480907
0.6737	Remote Similarity	NPC236973
0.6737	Remote Similarity	NPC32177
0.6737	Remote Similarity	NPC469756
0.6737	Remote Similarity	NPC275901
0.6667	Remote Similarity	NPC480910
0.6667	Remote Similarity	NPC240070
0.6667	Remote Similarity	NPC480909
0.6634	Remote Similarity	NPC475590
0.6632	Remote Similarity	NPC30483
0.6632	Remote Similarity	NPC470897
0.663	Remote Similarity	NPC250556
0.6602	Remote Similarity	NPC117445
0.6602	Remote Similarity	NPC308262
0.6602	Remote Similarity	NPC486134
0.6602	Remote Similarity	NPC486141
0.6598	Remote Similarity	NPC475629
0.6562	Remote Similarity	NPC292467
0.6522	Remote Similarity	NPC76572
0.6522	Remote Similarity	NPC193382
0.6495	Remote Similarity	NPC486130
0.6429	Remote Similarity	NPC486127
0.6383	Remote Similarity	NPC483822
0.6374	Remote Similarity	NPC99620
0.6327	Remote Similarity	NPC475556
0.6327	Remote Similarity	NPC311706
0.6304	Remote Similarity	NPC84987
0.6263	Remote Similarity	NPC231518
0.6263	Remote Similarity	NPC488944
0.6238	Remote Similarity	NPC247190
0.6237	Remote Similarity	NPC480915
0.6211	Remote Similarity	NPC179412
0.6211	Remote Similarity	NPC471356
0.62	Remote Similarity	NPC208193
0.617	Remote Similarity	NPC84949
0.617	Remote Similarity	NPC480562
0.617	Remote Similarity	NPC74945
0.617	Remote Similarity	NPC31354
0.617	Remote Similarity	NPC69576
0.6162	Remote Similarity	NPC32793
0.6162	Remote Similarity	NPC116075
0.6117	Remote Similarity	NPC476221
0.6117	Remote Similarity	NPC477709
0.6117	Remote Similarity	NPC486132
0.6117	Remote Similarity	NPC486131
0.6058	Remote Similarity	NPC486128
0.6	Remote Similarity	NPC329636
0.598	Remote Similarity	NPC469749
0.5918	Remote Similarity	NPC72260
0.5905	Remote Similarity	NPC479360
0.5905	Remote Similarity	NPC479359
0.5905	Remote Similarity	NPC488943
0.5905	Remote Similarity	NPC488942
0.5876	Remote Similarity	NPC305574
0.5851	Remote Similarity	NPC471633
0.5833	Remote Similarity	NPC486140
0.5789	Remote Similarity	NPC196429
0.5784	Remote Similarity	NPC610296
0.578	Remote Similarity	NPC486133
0.5755	Remote Similarity	NPC488938
0.5755	Remote Similarity	NPC488937
0.5729	Remote Similarity	NPC17896
0.5729	Remote Similarity	NPC469755
0.5729	Remote Similarity	NPC284406
0.5729	Remote Similarity	NPC197707
0.5729	Remote Similarity	NPC251866
0.5728	Remote Similarity	NPC55532
0.5714	Remote Similarity	NPC484202
0.5714	Remote Similarity	NPC471353
0.5686	Remote Similarity	NPC479353
0.5686	Remote Similarity	NPC479354
0.567	Remote Similarity	NPC199428
0.567	Remote Similarity	NPC109448
0.567	Remote Similarity	NPC310341
0.566	Remote Similarity	NPC475219
0.5631	Remote Similarity	NPC488941
0.5631	Remote Similarity	NPC488940
0.5612	Remote Similarity	NPC180079
0.5586	Remote Similarity	NPC488945
0.5586	Remote Similarity	NPC488946
0.5567	Remote Similarity	NPC157376
0.5567	Remote Similarity	NPC142066
0.5567	Remote Similarity	NPC603972
0.5526	Remote Similarity	NPC486152
0.5521	Remote Similarity	NPC99728
0.5521	Remote Similarity	NPC87250
0.5521	Remote Similarity	NPC244402
0.5521	Remote Similarity	NPC50305
0.5429	Remote Similarity	NPC59288
0.5408	Remote Similarity	NPC34390
0.54	Remote Similarity	NPC93883
0.5398	Remote Similarity	NPC488947
0.5385	Remote Similarity	NPC608063
0.537	Remote Similarity	NPC479357
0.5361	Remote Similarity	NPC473852
0.5354	Remote Similarity	NPC243196
0.5333	Remote Similarity	NPC264336
0.5327	Remote Similarity	NPC488939
0.5306	Remote Similarity	NPC219085
0.53	Remote Similarity	NPC146456
0.53	Remote Similarity	NPC88668
0.5146	Remote Similarity	NPC488161
0.5146	Remote Similarity	NPC16569
0.5143	Remote Similarity	NPC40749
0.5111	Remote Similarity	NPC196931
0.5102	Remote Similarity	NPC158344
0.5102	Remote Similarity	NPC474418
0.51	Remote Similarity	NPC99080
0.5098	Remote Similarity	NPC277374
0.5096	Remote Similarity	NPC173555
0.505	Remote Similarity	NPC10823
0.505	Remote Similarity	NPC604978
0.5043	Remote Similarity	NPC286809

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC329986 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5920
0.1-0.2	3129
0.2-0.3	83
0.3-0.4	4
0.4-0.5	7
0.5-0.6	5
0.6-0.7	2
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
0.663	Remote Similarity	NPD7507	Pre-clinical
0.6263	Remote Similarity	NPD8033	Approved
0.5918	Remote Similarity	NPD8294	Phase 4
0.5729	Remote Similarity	NPD7319	Approved
0.5728	Remote Similarity	NPD8377	Phase 4
0.53	Remote Similarity	NPD8335	Phase 4
0.5096	Remote Similarity	NPD8296	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