NPASS Compound

Natural Product: NPC275901

Natural Product ID	NPC275901
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OFSZOCPGPLMCBG-XAOCMOARSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101937787
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 -4.7655 0.6544 3.0852 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2735 0.9483 1.6677 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0557 0.1288 0.6684 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1856 -0.2030 -0.5352 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1493 0.8754 -0.7463 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2972 1.0388 0.4569 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.9328 0.7465 1.6099 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1253 0.3360 0.2409 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0197 1.0576 0.1362 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0959 0.7083 1.1072 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8744 -0.5084 0.7923 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4814 -0.5501 -0.6025 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9158 -1.7859 -1.2558 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2113 -2.9614 -0.5776 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0237 0.7132 -1.2792 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5777 0.8432 -2.6762 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0398 0.6365 -2.7657 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6939 -0.2277 -1.7663 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9568 -0.4968 -0.4903 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5578 -1.7921 0.0368 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0085 -1.6716 0.2590 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7336 -0.5123 -0.3163 C 0 0 2 0 0 0 0 0 0 0 0 0 8.1116 -1.0147 -0.7480 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0371 0.5447 0.7485 C 0 0 2 0 0 0 0 0 0 0 0 0 7.2041 1.8321 -0.0009 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2571 1.6429 -1.1682 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1240 0.1954 -1.4603 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8162 -0.0674 -2.6710 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2596 0.2582 1.5247 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3842 0.9834 1.6136 C 0 0 0 0 0 0 0 0 0 0 0 0 10.3445 0.3489 2.4828 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5047 0.8015 2.7606 O 0 0 0 0 0 0 0 0 0 0 0 0 9.7853 -0.8060 2.9420 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5098 -0.9360 2.4018 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5276 0.8996 -1.2827 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7634 2.0981 -1.0376 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0157 -0.2164 -1.6516 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2175 0.7556 0.2543 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3774 0.0339 0.5281 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.3531 0.9364 1.2119 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.7044 0.2702 1.3747 C 0 0 2 0 0 0 0 0 0 0 0 0 -10.1570 -0.4001 0.0955 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.0060 -1.2228 -0.4089 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.4317 -2.0073 -1.6304 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4746 -2.8663 -1.3605 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9664 -0.3735 -0.7000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.2750 -1.1669 0.4092 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.6335 1.2581 1.7122 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8884 1.2661 2.4621 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5803 -0.1105 3.0305 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2120 1.5517 3.5599 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9330 0.3107 3.7327 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5032 2.0149 1.4743 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3198 -0.8273 1.1445 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6819 -1.1682 -0.4683 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5383 0.6204 -1.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9887 2.1299 0.4989 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2170 2.1343 0.2567 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6620 0.5683 2.1218 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7745 1.5793 1.2093 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7006 -0.5748 1.5526 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2396 -1.3987 1.0126 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2697 -1.9254 -2.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8103 -1.7307 -1.3073 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4674 -3.5608 -0.4366 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4471 1.5600 -0.7009 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0727 0.0462 -3.2856 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2622 1.7999 -3.1405 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5031 1.6714 -2.8021 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2486 0.2659 -3.8173 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8237 -1.2414 -2.2652 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1869 0.2523 0.3034 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9463 -2.1645 0.8530 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4323 -2.5094 -0.8343 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5438 -2.6303 -0.0091 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1610 -1.6183 1.3815 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2218 -0.9274 -1.8452 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9420 -0.4406 -0.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1760 -2.1003 -0.5331 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2136 0.6188 1.5007 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9728 2.7266 0.5991 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2317 1.9777 -0.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7127 2.1581 -2.0350 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2946 2.1650 -0.9924 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4454 -0.9060 -3.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5757 1.9200 1.1153 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4905 -1.8884 1.8272 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7833 -0.9401 3.2459 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 0.0669 -1.8235 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3276 1.8011 -1.9011 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8383 2.2170 -2.0224 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5673 0.6167 -1.6628 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1766 -0.9207 1.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4301 1.8603 0.5980 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6046 -0.4708 2.2096 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4830 0.3887 -0.6078 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7622 -1.9625 0.3792 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7667 -1.3312 -2.4580 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5868 -2.6132 -2.0282 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4769 -3.2214 -0.4353 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1228 -0.6863 0.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6138 1.9474 1.0081 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5473 1.8742 2.8756 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 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 6 13 14 1 0 12 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 0 21 22 1 0 22 23 1 6 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 6 24 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 15 35 1 0 5 36 1 0 4 37 1 0 3 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 43 46 1 0 42 47 1 0 41 48 1 0 40 49 1 0 7 2 1 0 35 9 1 0 46 39 1 0 19 12 1 0 27 22 1 0 34 29 1 0 27 18 1 0 1 50 1 0 1 51 1 0 1 52 1 0 2 53 1 6 3 54 1 1 4 55 1 1 5 56 1 6 6 57 1 1 9 58 1 1 10 59 1 0 10 60 1 0 11 61 1 0 11 62 1 0 13 63 1 0 13 64 1 0 14 65 1 0 15 66 1 1 16 67 1 0 16 68 1 0 17 69 1 0 17 70 1 0 18 71 1 6 19 72 1 1 20 73 1 0 20 74 1 0 21 75 1 0 21 76 1 0 23 77 1 0 23 78 1 0 23 79 1 0 24 80 1 1 25 81 1 0 25 82 1 0 26 83 1 0 26 84 1 0 28 85 1 0 30 86 1 0 34 87 1 0 34 88 1 0 35 89 1 0 35 90 1 0 36 91 1 0 37 92 1 0 39 93 1 1 40 94 1 6 41 95 1 1 42 96 1 6 43 97 1 1 44 98 1 0 44 99 1 0 45100 1 0 47101 1 0 48102 1 0 49103 1 0 M END

Standard InCHIKey	OFSZOCPGPLMCBG-XAOCMOARSA-N
Standard InCHI	InChI=1S/C35H54O14/c1-16-30(49-32-28(42)26(40)25(39)23(13-36)48-32)27(41)29(43)31(46-16)47-19-5-9-34(15-37)18(12-19)3-4-22-21(34)6-8-33(2)20(7-10-35(22,33)44)17-11-24(38)45-14-17/h11,16,18-23,25-32,36-37,39-44H,3-10,12-15H2,1-2H3/t16-,18+,19+,20-,21+,22-,23-,25-,26+,27+,28-,29-,30-,31+,32+,33-,34-,35+/m1/s1
SMILES	C[C@@H]1[C@H]([C@H]([C@H]([C@@H](O1)O[C@H]1CC[C@@]2(CO)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@H](CC[C@]32O)C2=CC(=O)OC2)C1)O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	698.35	Volume:	671.811 ? Van der Waals volume.
Dense:	1.04	LogP:	-0.557 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.215 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.83 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	38.0
TPSA:	225.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	8.0	Rings:	7.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.121	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.678	Fsp³:	0.914
MCE-18:	133.284 ? 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:	0.717	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.012 ? 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:	0.148	Promiscuous compounds:	0.27

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.56	MDCK Permeability:	-5.184
Pgp-inhibitor:	0.0	Pgp-substrate:	0.974
PAMPA:	1.0 ? 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):	0.053
20% Bioavailability (F20%):	0.229	30% Bioavailability (F30%):	0.936
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.1
Plasma Protein Binding (PPB):	58.106%	Volume Distribution (VD):	-0.468
Fu:	38.962% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.013
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.808	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.043
HLM stability:	0.001 ? 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):

0.548

Half-life (T1/2):

3.459

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.228
Human Hepatotoxicity (H-HT):	0.753	Drug-induced Liver Injury (DILI):	0.956
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.617
Maximum Recommended Daily Dose:	0.988	Skin Sensitization:	1.0
Carcinogencity:	0.601	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.686
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.989
Hematotoxicity:	0.831	Drug-induced Nephrotoxicity:	0.993
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.841
A549 Cytotoxicity:	0.751	Hek293 Cytotoxicity:	0.972
BCF:	0.675 ? 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:	3.202 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.472 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.648 ? 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
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	leaves	n.a.	n.a.	PMID[16933890]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	root	n.a.	PMID[19052526]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28817274]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31967821]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32649211]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9548837]
NPO30295	Calotropis gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	3
Ratio IC50	1
EC50	1

Activity Type	# Activity
Cell line	3
Others	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
NPT457	Cell line	BT-549	Homo sapiens	IC50	=	70.0	nM	PMID[32649211]
NPT402	Cell line	Hs-578T	Homo sapiens	IC50	=	300.0	nM	PMID[32649211]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	980.0	nM	PMID[32649211]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	14.0	n.a.	PMID[32649211]
NPT2	Others	Unspecified	n.a.	EC50	=	600.0	nM	PMID[32649211]

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 NPC275901 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	14909
0.1-0.2	29040
0.2-0.3	4759
0.3-0.4	927
0.4-0.5	75
0.5-0.6	72
0.6-0.7	46
0.7-0.8	0
0.8-0.85	6
0.85-0.9	4
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC32177
1.0	High Similarity	NPC469756
0.8961	High Similarity	NPC77299
0.8961	High Similarity	NPC480906
0.878	High Similarity	NPC236973
0.8675	High Similarity	NPC188234
0.8471	Intermediate Similarity	NPC486135
0.8471	Intermediate Similarity	NPC486137
0.8148	Intermediate Similarity	NPC76572
0.8148	Intermediate Similarity	NPC193382
0.8023	Intermediate Similarity	NPC480910
0.8023	Intermediate Similarity	NPC480909
0.7912	Intermediate Similarity	NPC486136
0.7805	Intermediate Similarity	NPC5311
0.7711	Intermediate Similarity	NPC480914
0.7614	Intermediate Similarity	NPC32793
0.7614	Intermediate Similarity	NPC116075
0.7558	Intermediate Similarity	NPC480907
0.7444	Intermediate Similarity	NPC486143
0.7444	Intermediate Similarity	NPC125077
0.7444	Intermediate Similarity	NPC486142
0.7444	Intermediate Similarity	NPC486149
0.7363	Intermediate Similarity	NPC232785
0.7363	Intermediate Similarity	NPC486139
0.7191	Intermediate Similarity	NPC30483
0.7191	Intermediate Similarity	NPC470897
0.7143	Intermediate Similarity	NPC264336
0.7033	Intermediate Similarity	NPC240070
0.701	Intermediate Similarity	NPC120390
0.6979	Remote Similarity	NPC486144
0.6979	Remote Similarity	NPC486145
0.6979	Remote Similarity	NPC486147
0.6979	Remote Similarity	NPC475590
0.6979	Remote Similarity	NPC486148
0.6941	Remote Similarity	NPC99620
0.6923	Remote Similarity	NPC292467
0.686	Remote Similarity	NPC84987
0.6782	Remote Similarity	NPC469750
0.6742	Remote Similarity	NPC471353
0.6742	Remote Similarity	NPC305574
0.6739	Remote Similarity	NPC40749
0.6737	Remote Similarity	NPC329986
0.6737	Remote Similarity	NPC140092
0.6737	Remote Similarity	NPC486146
0.6702	Remote Similarity	NPC59288
0.6667	Remote Similarity	NPC475556
0.6667	Remote Similarity	NPC74259
0.6667	Remote Similarity	NPC486138
0.6667	Remote Similarity	NPC276838
0.6667	Remote Similarity	NPC311706
0.6596	Remote Similarity	NPC475629
0.6556	Remote Similarity	NPC483822
0.6526	Remote Similarity	NPC208193
0.6489	Remote Similarity	NPC486130
0.6421	Remote Similarity	NPC486127
0.6408	Remote Similarity	NPC474423
0.6337	Remote Similarity	NPC475419
0.6292	Remote Similarity	NPC196429
0.6275	Remote Similarity	NPC474908
0.6275	Remote Similarity	NPC486134
0.6275	Remote Similarity	NPC486141
0.625	Remote Similarity	NPC231518
0.625	Remote Similarity	NPC488944
0.6222	Remote Similarity	NPC157376
0.6222	Remote Similarity	NPC142066
0.6222	Remote Similarity	NPC603972
0.6214	Remote Similarity	NPC486150
0.61	Remote Similarity	NPC486132
0.61	Remote Similarity	NPC486131
0.6064	Remote Similarity	NPC72260
0.604	Remote Similarity	NPC486128
0.6	Remote Similarity	NPC99728
0.6	Remote Similarity	NPC87250
0.6	Remote Similarity	NPC244402
0.6	Remote Similarity	NPC50305
0.596	Remote Similarity	NPC469749
0.5941	Remote Similarity	NPC475219
0.59	Remote Similarity	NPC146857
0.5882	Remote Similarity	NPC479360
0.5882	Remote Similarity	NPC479359
0.5882	Remote Similarity	NPC488943
0.5882	Remote Similarity	NPC488942
0.587	Remote Similarity	NPC17896
0.587	Remote Similarity	NPC469755
0.587	Remote Similarity	NPC284406
0.587	Remote Similarity	NPC197707
0.587	Remote Similarity	NPC251866
0.587	Remote Similarity	NPC480915
0.5824	Remote Similarity	NPC471633
0.581	Remote Similarity	NPC486140
0.581	Remote Similarity	NPC117445
0.581	Remote Similarity	NPC329675
0.581	Remote Similarity	NPC308262
0.5806	Remote Similarity	NPC243196
0.5784	Remote Similarity	NPC476221
0.5784	Remote Similarity	NPC477709
0.5758	Remote Similarity	NPC610296
0.5755	Remote Similarity	NPC486133
0.5743	Remote Similarity	NPC247190
0.5714	Remote Similarity	NPC222875
0.5714	Remote Similarity	NPC25177
0.5684	Remote Similarity	NPC179412
0.5684	Remote Similarity	NPC471356
0.5657	Remote Similarity	NPC479353
0.5657	Remote Similarity	NPC479354
0.5638	Remote Similarity	NPC199428
0.5638	Remote Similarity	NPC109448
0.5638	Remote Similarity	NPC310341
0.56	Remote Similarity	NPC488941
0.56	Remote Similarity	NPC488940
0.5579	Remote Similarity	NPC146456
0.5579	Remote Similarity	NPC250556
0.5556	Remote Similarity	NPC488945
0.5556	Remote Similarity	NPC488946
0.5545	Remote Similarity	NPC55532
0.5543	Remote Similarity	NPC158344
0.5514	Remote Similarity	NPC194716
0.5495	Remote Similarity	NPC486152
0.5474	Remote Similarity	NPC84949
0.5474	Remote Similarity	NPC480562
0.5474	Remote Similarity	NPC74945
0.5474	Remote Similarity	NPC31354
0.5474	Remote Similarity	NPC69576
0.5429	Remote Similarity	NPC488938
0.5429	Remote Similarity	NPC488937
0.5426	Remote Similarity	NPC219085
0.5412	Remote Similarity	NPC480913
0.5408	Remote Similarity	NPC329905
0.5361	Remote Similarity	NPC93883
0.5347	Remote Similarity	NPC608063
0.5333	Remote Similarity	NPC479357
0.5321	Remote Similarity	NPC329784
0.5319	Remote Similarity	NPC473852
0.5268	Remote Similarity	NPC286809
0.5263	Remote Similarity	NPC309034
0.5248	Remote Similarity	NPC27363
0.5204	Remote Similarity	NPC484202
0.52	Remote Similarity	NPC173555
0.5152	Remote Similarity	NPC471354
0.5152	Remote Similarity	NPC27507
0.5143	Remote Similarity	NPC488939
0.5102	Remote Similarity	NPC77319
0.5102	Remote Similarity	NPC471351
0.5102	Remote Similarity	NPC471355
0.5089	Remote Similarity	NPC488947
0.5055	Remote Similarity	NPC473555
0.5053	Remote Similarity	NPC474418

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC275901 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6093
0.1-0.2	2945
0.2-0.3	87
0.3-0.4	9
0.4-0.5	8
0.5-0.6	6
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
0.625	Remote Similarity	NPD8033	Approved
0.6064	Remote Similarity	NPD8294	Phase 4
0.587	Remote Similarity	NPD7319	Approved
0.5579	Remote Similarity	NPD7507	Pre-clinical
0.5545	Remote Similarity	NPD8377	Phase 4
0.52	Remote Similarity	NPD8296	Phase 4
0.5102	Remote Similarity	NPD8335	Phase 4
0.5051	Remote Similarity	NPD8380	Approved

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