NPASS Compound

Natural Product: NPC478080

Natural Product ID	NPC478080
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl (1S,12R,14R,15E,18S)-15-ethylidene-12-[(1R,15S,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraen-6-yl]-18-(hydroxymethyl)-17-methyl-10,17-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8-tetraene-18-carboxylate
IUPAC Name	methyl (1S,12R,14R,15E,18S)-15-ethylidene-12-[(1R,15S,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraen-6-yl]-18-(hydroxymethyl)-17-methyl-10,17-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8-tetraene-18-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	122179185
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002748] Ibogan-type alkaloids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 102110 0 0 0 0 0 0 0 0999 V2000 1.3592 8.1775 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1208 6.6966 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8825 5.2157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3823 5.2381 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1517 3.9504 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4212 2.6403 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9214 2.6179 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1520 3.9056 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3344 4.1069 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.8796 4.7453 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4186 3.0703 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2841 1.5763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2760 0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3943 -1.2135 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 -2.6807 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4086 -3.6844 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8351 -3.2209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1470 -1.7537 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0323 -0.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9499 -4.2246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3764 -3.7611 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0967 -5.1517 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5946 -5.0732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7093 -6.0769 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0654 -6.7412 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2060 -5.7670 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9326 -4.2921 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3387 -8.2161 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1981 -9.1902 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7842 -8.6895 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7878 -7.5748 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6048 -8.8328 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4218 -10.0908 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2144 -7.1113 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5389 -7.8154 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5263 -5.6441 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9529 -5.1805 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2862 -8.7680 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8285 -7.7643 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9070 -6.2664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3559 -5.8782 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1729 -7.1362 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6544 -7.3708 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1919 -8.7712 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2480 -9.9369 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7664 -9.7022 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2289 -8.3019 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4715 -10.6651 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1218 8.4159 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8401 7.9392 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5975 9.6585 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3601 6.9350 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6154 6.8237 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5346 5.7076 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2815 6.7347 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7085 5.9390 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6515 3.9729 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8382 2.1484 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1828 1.1594 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5359 2.2623 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6341 3.6745 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1231 5.5840 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9560 5.9272 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1880 4.3580 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8911 2.7841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7840 1.5950 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8112 0.1720 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7760 0.0000 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 -3.1443 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5736 -1.2902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5745 -4.6636 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7425 -2.4016 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7359 -3.1271 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2398 -4.4707 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0619 -4.7614 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4901 -3.5768 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9744 -5.2709 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5484 -6.4363 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4075 -4.0188 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6537 -5.0760 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8411 -2.7949 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5127 -9.1497 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7973 -7.8659 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2601 -10.1120 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4558 -9.7970 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0721 -8.5211 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9197 -10.0123 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0315 -3.6826 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5869 -6.5400 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3795 -4.7170 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9718 -9.5850 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7497 -10.1946 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8935 -4.4778 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5984 -6.2051 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6735 -9.0058 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7855 -11.3373 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8225 -10.8680 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9966 -10.9385 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9463 -10.9386 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7448 -12.1400 0.0000 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 9 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 19 22 1 0 22 23 1 0 18 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 27 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 6 34 35 1 0 33 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 32 40 1 0 40 41 1 0 41 42 2 0 42 43 1 0 43 44 1 0 44 45 2 0 45 46 1 0 46 47 2 0 47 48 1 0 48 49 2 0 31 50 1 0 8 3 1 0 10 5 1 0 14 7 1 0 21 13 1 0 21 16 1 0 42 24 1 0 33 26 1 0 49 41 1 0 49 44 1 0 1 51 1 0 1 52 1 0 1 53 1 0 2 54 1 0 2 55 1 0 3 56 1 6 4 57 1 0 4 58 1 0 5 59 1 6 6 60 1 0 6 61 1 0 7 62 1 6 8 63 1 6 10 64 1 0 10 65 1 0 11 66 1 0 11 67 1 0 12 68 1 0 12 69 1 0 15 70 1 0 17 71 1 0 20 72 1 0 23 73 1 0 23 74 1 0 23 75 1 0 24 76 1 1 25 77 1 0 25 78 1 0 26 79 1 6 28 80 1 0 29 81 1 0 29 82 1 0 29 83 1 0 30 84 1 0 30 85 1 0 32 86 1 1 34 87 1 0 34 88 1 0 35 89 1 0 39 90 1 0 39 91 1 0 39 92 1 0 40 93 1 0 40 94 1 0 43 95 1 0 45 96 1 0 46 97 1 0 47 98 1 0 48 99 1 0 50100 1 0 50101 1 0 50102 1 0 M END

Standard InCHIKey	FEQZUIYQDAAUOE-UMXRBDIUSA-N
Standard InCHI	InChI=1S/C42H52N4O4/c1-6-24-14-23-15-32-38-27(12-13-46(20-23)40(24)32)28-18-36(49-4)29(17-35(28)44-38)30-16-33-25(7-2)21-45(3)37(42(33,22-47)41(48)50-5)19-31-26-10-8-9-11-34(26)43-39(30)31/h7-11,17-18,23-24,30,32-33,37,40,43-44,47H,6,12-16,19-22H2,1-5H3/b25-7-/t23-,24-,30+,32-,33+,37-,40-,42-/m0/s1
SMILES	CC[C@H]1C[C@H]2C[C@@H]3[C@H]1N(C2)CCC4=C3NC5=CC(=C(C=C45)OC)[C@H]6C[C@@H]7/C(=C\C)/CN([C@H]([C@@]7(CO)C(=O)OC)CC8=C6NC9=CC=CC=C89)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	676.4	Volume:	710.763 ? Van der Waals volume.
Dense:	0.952	LogP:	4.444 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.434 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.956 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	46.0
TPSA:	93.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	10.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.165	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.565	Fsp³:	0.548
MCE-18:	178.108 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.941	Fluc inhibitor:	0.035 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.911 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.742 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.001	Promiscuous compounds:	0.966

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.183	MDCK Permeability:	-4.911
Pgp-inhibitor:	0.266	Pgp-substrate:	0.593
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%):	0.001	30% Bioavailability (F30%):	0.25
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.976
Plasma Protein Binding (PPB):	94.974%	Volume Distribution (VD):	0.811
Fu:	4.147% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	1.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.877	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.99
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.237
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.949
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.072 ? 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):

9.668

Half-life (T1/2):

0.913

ADMET: Toxicity

hERG Blockers:	0.836	hERG Blockers (10um):	0.661
Human Hepatotoxicity (H-HT):	0.94	Drug-induced Liver Injury (DILI):	0.843
AMES Toxicity:	0.43	Rat Oral Acute Toxicity:	0.95
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	0.908
Carcinogencity:	0.763	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.998
Drug-induced Neurotoxicity:	0.958	Ototoxicity:	0.99
Hematotoxicity:	0.541	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.995	RPMI-8226 Immunitoxicity:	0.332
A549 Cytotoxicity:	0.915	Hek293 Cytotoxicity:	0.941
BCF:	2.486 ? 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:	5.094 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.607 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.369 ? 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
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	PMID[18778099]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[24773071]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	stem-bark	Pahang, Malaysia	2003-JUN	PMID[25919190]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26918761]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27077800]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29319316]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30869890]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32356659]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9376	Tabernaemontana corymbosa	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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	8
Activity	18

Activity Type	# Activity
Cell line	26

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
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	2910	nM	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	IC50	=	2770	nM	PMID[25919190]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	4190	nM	PMID[25919190]
NPT81	Cell line	A549	Homo sapiens	IC50	=	3060	nM	PMID[25919190]
NPT91	Cell line	KB	Homo sapiens	IC50	=	980	nM	PMID[25919190]
NPT91	Cell line	KB	Homo sapiens	IC50	=	1210	nM	PMID[25919190]
NPT91	Cell line	KB	Homo sapiens	IC50	=	1390	nM	PMID[25919190]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	2570	nM	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	80	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	35	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	6.98	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	11.4	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	3	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	79.6	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	8.25	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	72.4	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	14.5	%	PMID[25919190]
NPT393	Cell line	HCT-116	Homo sapiens	Activity	=	4.85	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	3.95	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	5.76	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	0.18	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	90.1	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	21.4	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	13.8	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	1.68	%	PMID[25919190]
NPT784	Cell line	MDA-MB-468	Homo sapiens	Activity	=	63.1	%	PMID[25919190]

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 NPC478080 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	16501
0.1-0.2	32584
0.2-0.3	578
0.3-0.4	122
0.4-0.5	35
0.5-0.6	22
0.6-0.7	11
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
0.7607	Intermediate Similarity	NPC485921
0.7607	Intermediate Similarity	NPC478082
0.7094	Intermediate Similarity	NPC485894
0.7049	Intermediate Similarity	NPC485889
0.6772	Remote Similarity	NPC488883
0.6639	Remote Similarity	NPC485890
0.6508	Remote Similarity	NPC478081
0.6484	Remote Similarity	NPC488882
0.6484	Remote Similarity	NPC485918
0.6484	Remote Similarity	NPC485915
0.6341	Remote Similarity	NPC29422
0.627	Remote Similarity	NPC485893
0.625	Remote Similarity	NPC485913
0.6045	Remote Similarity	NPC485919
0.6045	Remote Similarity	NPC485920
0.594	Remote Similarity	NPC605382
0.5912	Remote Similarity	NPC485914
0.5859	Remote Similarity	NPC485897
0.5859	Remote Similarity	NPC485896
0.5854	Remote Similarity	NPC485962
0.5854	Remote Similarity	NPC477065
0.5852	Remote Similarity	NPC485943
0.5821	Remote Similarity	NPC485912
0.5683	Remote Similarity	NPC485934
0.5352	Remote Similarity	NPC485952
0.5344	Remote Similarity	NPC17437
0.527	Remote Similarity	NPC488873
0.5263	Remote Similarity	NPC485949
0.5248	Remote Similarity	NPC485917
0.5248	Remote Similarity	NPC485954
0.5211	Remote Similarity	NPC485911
0.5189	Remote Similarity	NPC21605
0.5189	Remote Similarity	NPC215538
0.5168	Remote Similarity	NPC488872
0.5137	Remote Similarity	NPC485942
0.5045	Remote Similarity	NPC329793
0.5045	Remote Similarity	NPC600762

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC478080 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4226
0.1-0.2	4837
0.2-0.3	70
0.3-0.4	15
0.4-0.5	0
0.5-0.6	2
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
0.5802	Remote Similarity	NPD8358	Approved
0.5045	Remote Similarity	NPD4118	Clinical (unspecified phase)

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